Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations

Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase–mediated hyperpermeability, a potential therapeutic target, has not been established. Methods: We analyzed PDC...

Full description

Saved in:
Bibliographic Details
Published inGenetics in medicine Vol. 17; no. 3; pp. 188 - 196
Main Authors Shenkar, Robert, Shi, Changbin, Rebeiz, Tania, Stockton, Rebecca A., McDonald, David A., Mikati, Abdul Ghani, Zhang, Lingjiao, Austin, Cecilia, Akers, Amy L., Gallione, Carol J., Rorrer, Autumn, Gunel, Murat, Min, Wang, Marcondes de Souza, Jorge, Lee, Connie, Marchuk, Douglas A., Awad, Issam A.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.03.2015
Elsevier Limited
Subjects
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
631/208/737
692/420/2489/144
692/699/375/1370
Adolescent
Adult
Animals
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Biomedicine
Carrier Proteins - genetics
Cells, Cultured
Central Nervous System Neoplasms - enzymology
Central Nervous System Neoplasms - genetics
Central Nervous System Neoplasms - pathology
Child
Child, Preschool
Disease Models, Animal
Hemangioma, Cavernous, Central Nervous System - enzymology
Hemangioma, Cavernous, Central Nervous System - genetics
Hemangioma, Cavernous, Central Nervous System - pathology
Human Genetics
Human Umbilical Vein Endothelial Cells
Humans
Infant
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Keratin-1 - genetics
Laboratory Medicine
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Middle Aged
Mutation
original-research-article
Prospective Studies
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
Stress Fibers - drug effects
Stress Fibers - metabolism
Young Adult
cerebral cavernous malformation
Rho kinase
vascular malformations
Online AccessGet full text
ISSN1098-3600
1530-0366
1530-0366
DOI10.1038/gim.2014.97

Cover

Abstract Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase–mediated hyperpermeability, a potential therapeutic target, has not been established. Methods: We analyzed PDCD10 small interfering RNA–treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. Results: We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. Conclusion: These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials. Genet Med 17 3, 188–196.
AbstractList Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established. Methods: We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. Results: We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. Conclusion: These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.
Purpose:The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.Methods:We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.Results:We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.Conclusion:These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.
The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established. We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.
Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase–mediated hyperpermeability, a potential therapeutic target, has not been established. Methods: We analyzed PDCD10 small interfering RNA–treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. Results: We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. Conclusion: These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials. Genet Med 17 3, 188–196.
The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.PURPOSEThe phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.METHODSWe analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.RESULTSWe determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.CONCLUSIONThese findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.
Author McDonald, David A.
Zhang, Lingjiao
Stockton, Rebecca A.
Shi, Changbin
Akers, Amy L.
Gallione, Carol J.
Shenkar, Robert
Rebeiz, Tania
Min, Wang
Lee, Connie
Awad, Issam A.
Mikati, Abdul Ghani
Rorrer, Autumn
Gunel, Murat
Austin, Cecilia
Marchuk, Douglas A.
Marcondes de Souza, Jorge
AuthorAffiliation 3 Department of Pediatrics, University of California at Los Angeles, Torrance, CA 90502, USA
7 Departments of Neurosurgery and Neurobiology, Yale University, New Haven, CT 06520, USA
2 Department of Neurology, The University of Chicago Medicine, Chicago, IL 60637, USA
6 Angioma Alliance, Norfolk, VA 23510, USA
8 Department of Pathology, Yale University, New Haven, CT 06520, USA
9 Department of Neurosurgery, School of Medicine, Federal University of Rio De Janeiro, Rio de Janeiro, Brazil
4 Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA
5 Center for Science, Math and Technology Education, North Carolina Central University, Durham, NC 27707, USA
1 Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, IL 60637, USA
AuthorAffiliation_xml – name: 6 Angioma Alliance, Norfolk, VA 23510, USA
– name: 3 Department of Pediatrics, University of California at Los Angeles, Torrance, CA 90502, USA
– name: 7 Departments of Neurosurgery and Neurobiology, Yale University, New Haven, CT 06520, USA
– name: 9 Department of Neurosurgery, School of Medicine, Federal University of Rio De Janeiro, Rio de Janeiro, Brazil
– name: 2 Department of Neurology, The University of Chicago Medicine, Chicago, IL 60637, USA
– name: 5 Center for Science, Math and Technology Education, North Carolina Central University, Durham, NC 27707, USA
– name: 4 Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA
– name: 8 Department of Pathology, Yale University, New Haven, CT 06520, USA
– name: 1 Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, IL 60637, USA
Author_xml – sequence: 1
  givenname: Robert
  surname: Shenkar
  fullname: Shenkar, Robert
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine
– sequence: 2
  givenname: Changbin
  surname: Shi
  fullname: Shi, Changbin
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine
– sequence: 3
  givenname: Tania
  surname: Rebeiz
  fullname: Rebeiz, Tania
  organization: Department of Neurology, The University of Chicago Medicine
– sequence: 4
  givenname: Rebecca A.
  surname: Stockton
  fullname: Stockton, Rebecca A.
  organization: Department of Pediatrics, University of California, Los Angeles
– sequence: 5
  givenname: David A.
  surname: McDonald
  fullname: McDonald, David A.
  organization: Department of Molecular Genetics and Microbiology, Duke University, Center for Science, Math and Technology Education, North Carolina Central University
– sequence: 6
  givenname: Abdul Ghani
  surname: Mikati
  fullname: Mikati, Abdul Ghani
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine
– sequence: 7
  givenname: Lingjiao
  surname: Zhang
  fullname: Zhang, Lingjiao
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine
– sequence: 8
  givenname: Cecilia
  surname: Austin
  fullname: Austin, Cecilia
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine
– sequence: 9
  givenname: Amy L.
  surname: Akers
  fullname: Akers, Amy L.
  organization: Angioma Alliance
– sequence: 10
  givenname: Carol J.
  surname: Gallione
  fullname: Gallione, Carol J.
  organization: Department of Molecular Genetics and Microbiology, Duke University
– sequence: 11
  givenname: Autumn
  surname: Rorrer
  fullname: Rorrer, Autumn
  organization: Department of Molecular Genetics and Microbiology, Duke University
– sequence: 12
  givenname: Murat
  surname: Gunel
  fullname: Gunel, Murat
  organization: Department of Neurosurgery and Neurobiology, Yale University
– sequence: 13
  givenname: Wang
  surname: Min
  fullname: Min, Wang
  organization: Department of Pathology, Yale University
– sequence: 14
  givenname: Jorge
  surname: Marcondes de Souza
  fullname: Marcondes de Souza, Jorge
  organization: Department of Neurosurgery, School of Medicine, Federal University of Rio de Janeiro
– sequence: 15
  givenname: Connie
  surname: Lee
  fullname: Lee, Connie
  organization: Angioma Alliance
– sequence: 16
  givenname: Douglas A.
  surname: Marchuk
  fullname: Marchuk, Douglas A.
  organization: Department of Molecular Genetics and Microbiology, Duke University
– sequence: 17
  givenname: Issam A.
  surname: Awad
  fullname: Awad, Issam A.
  email: iawad@uchicago.edu
  organization: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Department of Neurology, The University of Chicago Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25122144$$D View this record in MEDLINE/PubMed
BookMark eNqNkstv1DAQxiNURB9w4o4icUGCLDN-JPGlEtqWh1QJDnC2HO8kdZXEi50s9L-vw5aqVCBxGkvz-z5945nj7GD0I2XZc4QVAq_fdm5YMUCxUtWj7AglhwJ4WR6kN6i64CXAYXYc4xUAVpzBk-yQSWQMhTjK2vOflraT86Ppc9N1gWJ0OxpTyX2bWwrUhNSyZkdh9HPMB9O3Pgxm0eQbF8lEyk2M3joz0Sb_4abL_MvZ-gwhH-bpFxefZo9b00d6dltPsm_vz7-uPxYXnz98Wr-7KKyo1FQwaZVqqhK5qDggklDQbEQjG2MZVYgIrSTDsG4bhky2CKknDJYVSdtyfpKd7n23czPQxtI4pfR6G9xgwrX2xuk_O6O71J3facGZQlTJ4NWtQfDfZ4qTHly01PdmpDS9xrIGUYKQ1X-gJShWShAJffkAvfJzSF-eqFqICqXExfDF_fB3qX9vKwGv94ANPsZA7R2CoJdb0OkW9HILWi12-IC2br-ONLnr_6F5s9fE5Dx2FO4F_Qt-A2boxn0
CitedBy_id crossref_primary_10_1001_jamaneurol_2018_3634
crossref_primary_10_1038_jcbfm_2015_98
crossref_primary_10_1002_mgg3_1794
crossref_primary_10_1038_nm_4169
crossref_primary_10_1016_j_mayocp_2019_11_005
crossref_primary_10_1002_mgg3_256
crossref_primary_10_1038_ncomms7449
crossref_primary_10_3171_2020_1_JNS193479
crossref_primary_10_1161_SVIN_123_001140
crossref_primary_10_1371_journal_pbio_3000051
crossref_primary_10_1007_s12975_023_01131_x
crossref_primary_10_3390_genes14020514
crossref_primary_10_1136_svn_2018_000195
crossref_primary_10_1007_s11886_017_0931_1
crossref_primary_10_1007_s00234_022_02958_1
crossref_primary_10_1007_s10571_022_01315_3
crossref_primary_10_1172_jci_insight_142838
crossref_primary_10_1016_j_jns_2024_123044
crossref_primary_10_2217_bmm_15_118
crossref_primary_10_1093_neuros_nyx091
crossref_primary_10_3389_fmolb_2021_622547
crossref_primary_10_1016_j_gendis_2020_12_008
crossref_primary_10_3389_fneur_2018_00953
crossref_primary_10_1016_j_eplepsyres_2022_106951
crossref_primary_10_1016_j_jaapos_2017_06_012
crossref_primary_10_1096_fj_201902888R
crossref_primary_10_1016_j_jneumeth_2016_06_021
crossref_primary_10_1515_medgen_2021_2091
crossref_primary_10_1007_s12975_024_01270_9
crossref_primary_10_1161_STROKEAHA_116_015013
crossref_primary_10_1016_j_gene_2024_148918
crossref_primary_10_5483_BMBRep_2016_49_5_036
crossref_primary_10_1007_s10456_020_09736_8
crossref_primary_10_1007_s00701_024_06378_3
crossref_primary_10_1093_neuros_nyaa478
crossref_primary_10_1098_rsob_200263
crossref_primary_10_1161_STROKEAHA_124_049935
crossref_primary_10_1007_s00701_024_06400_8
crossref_primary_10_1093_neuros_nyy108
crossref_primary_10_1161_STROKEAHA_119_027207
crossref_primary_10_1007_s10456_021_09809_2
crossref_primary_10_1016_j_wneu_2022_11_042
crossref_primary_10_1172_JCI144893
crossref_primary_10_15252_emmm_201809155
crossref_primary_10_3171_2016_5_JNS16687
crossref_primary_10_1111_jcmm_14773
crossref_primary_10_1016_j_wneu_2015_10_086
crossref_primary_10_1136_svn_2023_003004
crossref_primary_10_1111_jon_13072
crossref_primary_10_1016_j_cub_2017_02_028
crossref_primary_10_1016_j_isci_2018_11_001
crossref_primary_10_1016_j_cancergen_2024_08_001
crossref_primary_10_3389_fimmu_2022_922281
crossref_primary_10_1182_blood_2018_06_856062
crossref_primary_10_1177_09727531241308346
crossref_primary_10_1242_jcs_216093
crossref_primary_10_1016_j_tice_2021_101528
crossref_primary_10_3390_jvd4010008
crossref_primary_10_1002_brb3_70223
crossref_primary_10_1161_ATVBAHA_121_316707
crossref_primary_10_1007_s12031_015_0606_6
crossref_primary_10_1038_s10038_022_01063_8
crossref_primary_10_1016_j_tranon_2021_101013
crossref_primary_10_1161_CIRCRESAHA_118_312680
crossref_primary_10_1007_s00234_022_03056_y
crossref_primary_10_1101_cshperspect_a041188
crossref_primary_10_1159_000446884
crossref_primary_10_1038_s41572_022_00337_x
crossref_primary_10_1073_pnas_1702942114
crossref_primary_10_1097_MD_0000000000019800
crossref_primary_10_1177_1756286420902664
crossref_primary_10_1007_s00234_017_1845_8
crossref_primary_10_1590_0004_282x20160054
crossref_primary_10_1007_s12031_017_0893_1
crossref_primary_10_1007_s10072_018_3674_x
crossref_primary_10_1007_s12975_022_01050_3
crossref_primary_10_1016_j_molmed_2020_03_003
crossref_primary_10_1186_s40478_019_0789_0
crossref_primary_10_3171_2019_3_JNS181724
crossref_primary_10_3389_fnins_2020_604350
crossref_primary_10_1002_path_4844
crossref_primary_10_3174_ajnr_A4724
crossref_primary_10_1002_mco2_70027
crossref_primary_10_1161_CIRCRESAHA_121_318174
crossref_primary_10_3390_cells10030704
crossref_primary_10_1007_s00018_022_04355_6
crossref_primary_10_1111_jcmm_14075
crossref_primary_10_1038_s41374_018_0030_y
crossref_primary_10_1126_scitranslmed_aaw3521
crossref_primary_10_1093_neuros_nyy539
crossref_primary_10_1186_s12885_015_1709_8
crossref_primary_10_1172_jci_insight_126167
crossref_primary_10_2174_0115672026304601240307051654
crossref_primary_10_1007_s11060_018_03017_7
crossref_primary_10_1002_jmri_26927
crossref_primary_10_2139_ssrn_3155876
crossref_primary_10_3389_fsurg_2016_00060
crossref_primary_10_1016_j_celrep_2018_08_039
crossref_primary_10_1161_STROKEAHA_118_022314
crossref_primary_10_1097_MOH_0000000000000338
crossref_primary_10_1161_STROKEAHA_118_024058
crossref_primary_10_1007_s11481_016_9670_0
crossref_primary_10_1007_s43657_021_00030_1
crossref_primary_10_1016_j_nec_2022_05_001
crossref_primary_10_1007_s00018_018_2934_5
crossref_primary_10_1073_pnas_1501352112
crossref_primary_10_3390_ijms23095000
crossref_primary_10_1042_BSR20231675
crossref_primary_10_1007_s12975_019_00725_8
crossref_primary_10_1016_j_pediatrneurol_2020_11_004
crossref_primary_10_3390_genes13060961
crossref_primary_10_3389_fcvm_2022_954780
crossref_primary_10_1016_j_jstrokecerebrovasdis_2024_107947
crossref_primary_10_3390_cancers14235986
crossref_primary_10_1186_s13578_020_00514_z
Cites_doi 10.1161/STROKEAHA.108.515544
10.1007/s00018-013-1532-9
10.1126/scitranslmed.3002761
10.1016/j.biocel.2013.11.021
10.1038/nm.1911
10.1002/ana.20947
10.1016/j.devcel.2013.09.021
10.1161/STROKEAHA.110.594929
10.1227/01.NEU.0000315862.24920.49
10.1016/S0076-6879(07)00414-4
10.1002/humu.9389
10.1242/dev.093526
10.1227/00006123-199510000-00001
10.1074/jbc.C109.097220
10.1074/jbc.M110.213777
10.1111/j.1468-3083.2009.03263.x
10.1161/STROKEAHA.108.538769
10.3171/2011.3.FOCUS1165
10.1016/j.abb.2011.01.018
10.1016/j.ydbio.2011.12.006
10.1111/j.1750-3639.2010.00441.x
10.1212/WNL.57.10.1825
10.1172/JCI44393
10.1227/01.NEU.0000249188.38409.03
10.3171/jns.1994.80.3.0422
10.1084/jem.20091258
10.1016/j.febslet.2005.10.055
10.1093/hmg/ddn430
10.1016/S1474-4422(12)70004-2
10.1242/jcs.061341
10.1038/nature12207
10.1161/01.STR.0000157586.20479.fd
10.1161/STROKEAHA.111.625467
10.1159/000341774
10.1111/jcmm.12022
10.1093/hmg/ddq433
10.1253/circj.CJ-10-0110
10.1111/j.1399-0004.2012.01892.x
10.1086/426952
ContentType Journal Article
Copyright American College of Medical Genetics and Genomics 2015
Copyright Nature Publishing Group Mar 2015
Copyright_xml – notice: American College of Medical Genetics and Genomics 2015
– notice: Copyright Nature Publishing Group Mar 2015
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7X7
7XB
88E
8FI
8FJ
8FK
ABUWG
AFKRA
BENPR
CCPQU
FYUFA
GHDGH
K9.
M0S
M1P
PHGZM
PHGZT
PJZUB
PKEHL
PPXIY
PQEST
PQQKQ
PQUKI
PRINS
7X8
8FD
FR3
P64
RC3
5PM
DOI 10.1038/gim.2014.97
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest Hospital Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central
ProQuest One Community College
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Health & Medical Complete (Alumni)
ProQuest Health & Medical Collection
Proquest Medical Database
ProQuest Central Premium
ProQuest One Academic
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
Technology Research Database
Engineering Research Database
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
ProQuest Central China
ProQuest Hospital Collection (Alumni)
ProQuest Central
ProQuest Health & Medical Complete
Health Research Premium Collection
ProQuest Medical Library
ProQuest One Academic UKI Edition
Health and Medicine Complete (Alumni Edition)
Health & Medical Research Collection
ProQuest Central (New)
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Medical Library (Alumni)
ProQuest Central (Alumni)
MEDLINE - Academic
Genetics Abstracts
Engineering Research Database
Technology Research Database
Biotechnology and BioEngineering Abstracts
DatabaseTitleList Genetics Abstracts
ProQuest One Academic Middle East (New)
MEDLINE

MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 3
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
Biology
EISSN 1530-0366
EndPage 196
ExternalDocumentID PMC4329119
4265482841
25122144
10_1038_gim_2014_97
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NINDS NIH HHS
  grantid: R01 NS077957
– fundername: NHLBI NIH HHS
  grantid: R01 HL115148
– fundername: NCI NIH HHS
  grantid: P30 CA014236
– fundername: NHLBI NIH HHS
  grantid: K01 HL092599
– fundername: NHLBI NIH HHS
  grantid: 5K01HL092599-04
– fundername: NINDS NIH HHS
  grantid: NS077957
– fundername: NCATS NIH HHS
  grantid: UL1 TR000430
– fundername: NIGMS NIH HHS
  grantid: T32 GM007754
GroupedDBID ---
.-D
..I
.GJ
08G
39C
4Q1
4Q2
4Q3
53G
5GY
5RE
5VS
70F
7X7
88E
8FI
8FJ
AAFWJ
AAKAS
AALRI
AAXUO
AAYEP
AAYWO
ABAWZ
ABJNI
ABLJU
ABUWG
ACGFO
ACGFS
ACKTT
ACRQY
ACVFH
ADBBV
ADBIZ
ADCNI
ADVLN
ADZCM
AE3
AEJRE
AENEX
AEUPX
AEXYK
AFETI
AFJKZ
AFKRA
AFPUW
AFSHS
AFTRI
AGAYW
AGCQF
AHMBA
AHSBF
AHVBC
AIGII
AILAN
AITUG
AIZYK
AJRNO
AKBMS
AKRWK
AKYEP
ALFFA
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
APXCP
AXYYD
BENPR
BKKNO
BPHCQ
BS7
BVXVI
CCPQU
CS3
DNIVK
DU5
EBS
EE.
EFKBS
EIOEI
EJD
EX3
F5P
FDB
FDQFY
FERAY
FIZPM
FSGXE
FYUFA
H0~
HMCUK
JF9
JG8
JK3
JSO
K-O
KD2
M1P
M41
N9A
NQJWS
N~M
OAG
OAH
ODA
OK1
OLG
OVD
OWU
OWV
OWW
OWX
OWY
OWZ
P-K
P2P
PHGZM
PHGZT
PJZUB
PPXIY
PQQKQ
PROAC
PSQYO
R58
RNT
RNTTT
ROL
S4R
SNYQT
SOHCF
SOJ
SRMVM
SWTZT
T8P
TAOOD
TBHMF
TDRGL
TEORI
TSG
UKHRP
VVN
W3M
WOQ
WOW
XXN
XYM
YFH
ZFV
AAYXX
CITATION
3V.
AAZLF
ACZOJ
ADHDB
AWKKM
CGR
CUY
CVF
ECM
EIF
NAO
NPM
SNX
7XB
8FK
K9.
PKEHL
PQEST
PQUKI
PRINS
7X8
8FD
FR3
P64
RC3
5PM
ID FETCH-LOGICAL-c479t-25c99b7613473011e490bd4b5bac2e71110f5ea218fb2125f10b5b4a167e5cf33
IEDL.DBID 7X7
ISSN 1098-3600
1530-0366
IngestDate Thu Aug 21 18:22:14 EDT 2025
Tue Aug 05 10:00:56 EDT 2025
Tue Aug 05 10:52:03 EDT 2025
Fri Jul 25 08:40:58 EDT 2025
Wed Feb 19 02:26:59 EST 2025
Tue Jul 01 02:59:06 EDT 2025
Thu Apr 24 23:10:03 EDT 2025
Mon Jul 21 06:06:54 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords cerebral cavernous malformation
Rho kinase
vascular malformations
Language English
License Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c479t-25c99b7613473011e490bd4b5bac2e71110f5ea218fb2125f10b5b4a167e5cf33
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
OpenAccessLink https://pubmed.ncbi.nlm.nih.gov/PMC4329119
PMID 25122144
PQID 1844715517
PQPubID 2043492
PageCount 9
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_4329119
proquest_miscellaneous_1680460457
proquest_miscellaneous_1660926504
proquest_journals_1844715517
pubmed_primary_25122144
crossref_primary_10_1038_gim_2014_97
crossref_citationtrail_10_1038_gim_2014_97
springer_journals_10_1038_gim_2014_97
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2015-03-01
PublicationDateYYYYMMDD 2015-03-01
PublicationDate_xml – month: 03
  year: 2015
  text: 2015-03-01
  day: 01
PublicationDecade 2010
PublicationPlace New York
PublicationPlace_xml – name: New York
– name: United States
– name: Bethesda
PublicationSubtitle Official journal of the American College of Medical Genetics and Genomics
PublicationTitle Genetics in medicine
PublicationTitleAbbrev Genet Med
PublicationTitleAlternate Genet Med
PublicationYear 2015
Publisher Nature Publishing Group US
Elsevier Limited
Publisher_xml – name: Nature Publishing Group US
– name: Elsevier Limited
References Maddaluno, Rudini, Cuttano (CR4) 2013; 498
Zhang, Tang, Zhang (CR37) 2013; 27
Maraire, Awad (CR1) 1995; 37
Grassie, Moffat, Walsh, MacDonald (CR27) 2011; 510
Gault, Sain, Hu, Awad (CR9) 2006; 59
Shenkar, Venkatasubramanian, Wyrwicz (CR29) 2008; 63
Riant, Bergametti, Fournier (CR12) 2013; 4
Denier, Labauge, Bergametti (CR11) 2006; 60
Chan, Drakos, Ruiz (CR16) 2011; 121
Zhou, Liao (CR35) 2010; 74
Sirvente, Enjolras, Wassef, Tournier-Lasserve, Labauge (CR33) 2009; 23
Shi, Shenkar, Du (CR38) 2009; 40
Al-Shahi Salman, Berg, Morrison, Awad (CR8) 2008; 39
Murányi, Derkach, Erdodi, Kiss, Ito, Hartshorne (CR28) 2005; 579
Gault, Shenkar, Recksiek, Awad (CR30) 2005; 36
Akers, Johnson, Steinberg, Zabramski, Marchuk (CR31) 2009; 18
Louvi, Nishimura, Günel (CR13) 2014; 141
Bacigaluppi, Retta, Pileggi (CR40) 2013; 83
Fisher, Boggon (CR39) 2014; 71
Labauge, Brunereau, Laberge, Houtteville (CR24) 2001; 57
McDonald, Shi, Shenkar (CR3) 2012; 43
Stockton, Shenkar, Awad, Ginsberg (CR15) 2010; 207
Bergametti, Denier, Labauge (CR2) 2005; 76
Liu, Liao (CR36) 2008; 439
Gross, Lin, Du, Day (CR23) 2011; 30
Al-Shahi Salman, Hall, Horne (CR7) 2012; 11
Fidalgo, Fraile, Pires, Force, Pombo, Zalvide (CR17) 2010; 123
Borikova, Dibble, Sciaky (CR14) 2010; 285
Ceccarelli, Laister, Mulligan (CR22) 2011; 286
Li, Whitehead (CR5) 2010; 41
Liquori, Berg, Squitieri (CR32) 2006; 27
Hwang, Pallas (CR20) 2014; 47
Zabramski, Wascher, Spetzler (CR25) 1994; 80
Yoruk, Gillers, Chi, Scott (CR19) 2012; 362
Whitehead, Chan, Navankasattusas (CR26) 2009; 15
Kondziolka, Monaco, Lunsford (CR6) 2013; 27
McDonald, Shenkar, Shi (CR21) 2011; 20
D’Angelo, Marini, Rinaldi (CR10) 2011; 21
You, Sandalcioglu, Dammann, Felbor, Sure, Zhu (CR18) 2013; 17
Huynh, Nishimura, Rana (CR34) 2011; 3
Kondziolka (10.1038/gim.2014.97_bb0035)
Zhou (10.1038/gim.2014.97_bb0180)
Zabramski (10.1038/gim.2014.97_bb0130)
Grassie (10.1038/gim.2014.97_bb0140)
Shi (10.1038/gim.2014.97_bb0195)
You (10.1038/gim.2014.97_bb0095)
Fisher (10.1038/gim.2014.97_bb0200)
Maraire (10.1038/gim.2014.97_bb0010)
Louvi (10.1038/gim.2014.97_bb0070)
Sirvente (10.1038/gim.2014.97_bb0170)
Société Française de Neurochirurgie (10.1038/gim.2014.97_bb0015)
Yoruk (10.1038/gim.2014.97_bb0100)
Fidalgo (10.1038/gim.2014.97_bb0090)
Liquori (10.1038/gim.2014.97_bb0165)
D’Angelo (10.1038/gim.2014.97_bb0055)
Huynh (10.1038/gim.2014.97_bb0175)
Chan (10.1038/gim.2014.97_bb0085)
Maddaluno (10.1038/gim.2014.97_bb0025)
Riant (10.1038/gim.2014.97_bb0065)
McDonald (10.1038/gim.2014.97_bb0020)
Borikova (10.1038/gim.2014.97_bb0075)
Ceccarelli (10.1038/gim.2014.97_bb0115)
Akers (10.1038/gim.2014.97_bb0160)
Murányi (10.1038/gim.2014.97_bb0145)
Zhang (10.1038/gim.2014.97_bb0190)
Hwang (10.1038/gim.2014.97_bb0105)
Gault (10.1038/gim.2014.97_bb0155)
Stockton (10.1038/gim.2014.97_bb0080)
Bacigaluppi (10.1038/gim.2014.97_bb0205)
Gross (10.1038/gim.2014.97_bb0120)
Scottish Audit of Intracranial Vascular Malformations (SAIVMs) collaborators (10.1038/gim.2014.97_bb0040)
Angioma Alliance Scientific Advisory Board (10.1038/gim.2014.97_bb0045)
Société Française de Neurochirurgie (10.1038/gim.2014.97_bb0060)
Gault (10.1038/gim.2014.97_bb0050)
Labauge (10.1038/gim.2014.97_bb0125)
Shenkar (10.1038/gim.2014.97_bb0150)
Liu (10.1038/gim.2014.97_bb0185)
Li (10.1038/gim.2014.97_bb0030)
Whitehead (10.1038/gim.2014.97_bb0135)
McDonald (10.1038/gim.2014.97_bb0110)
References_xml – volume: 39
  start-page: 3222
  year: 2008
  end-page: 3230
  ident: CR8
  article-title: Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board
  publication-title: Stroke
  doi: 10.1161/STROKEAHA.108.515544
– volume: 71
  start-page: 1881
  year: 2014
  end-page: 1892
  ident: CR39
  article-title: Signaling pathways and the cerebral cavernous malformations proteins: lessons from structural biology
  publication-title: Cell Mol Life Sci
  doi: 10.1007/s00018-013-1532-9
– volume: 3
  start-page: 112ra122
  year: 2011
  ident: CR34
  article-title: Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration
  publication-title: Sci Transl Med
  doi: 10.1126/scitranslmed.3002761
– volume: 47
  start-page: 118
  year: 2014
  end-page: 148
  ident: CR20
  article-title: STRIPAK complexes: structure, biological function, and involvement in human diseases
  publication-title: Int J Biochem Cell Biol
  doi: 10.1016/j.biocel.2013.11.021
– volume: 15
  start-page: 177
  year: 2009
  end-page: 184
  ident: CR26
  article-title: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases
  publication-title: Nat Med
  doi: 10.1038/nm.1911
– volume: 4
  start-page: 165
  year: 2013
  end-page: 172
  ident: CR12
  article-title: CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas
  publication-title: Mol Syndromol
– volume: 60
  start-page: 550
  year: 2006
  end-page: 556
  ident: CR11
  article-title: Genotype-phenotype correlations in cerebral cavernous malformations patients
  publication-title: Ann Neurol
  doi: 10.1002/ana.20947
– volume: 27
  start-page: 215
  year: 2013
  end-page: 226
  ident: CR37
  article-title: A network of interactions enables CCM3 and STK24 to coordinate UNC13D-driven vesicle exocytosis in neutrophils
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2013.09.021
– volume: 41
  start-page: S92
  issue: 10 Suppl
  year: 2010
  end-page: S94
  ident: CR5
  article-title: Evaluating strategies for the treatment of cerebral cavernous malformations
  publication-title: Stroke
  doi: 10.1161/STROKEAHA.110.594929
– volume: 63
  start-page: 790
  year: 2008
  end-page: 7; discussion 797
  ident: CR29
  article-title: Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models
  publication-title: Neurosurgery
  doi: 10.1227/01.NEU.0000315862.24920.49
– volume: 439
  start-page: 181
  year: 2008
  end-page: 189
  ident: CR36
  article-title: A method for measuring Rho kinase activity in tissues and cells
  publication-title: Methods Enzymol
  doi: 10.1016/S0076-6879(07)00414-4
– volume: 27
  start-page: 118
  year: 2006
  ident: CR32
  article-title: Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus
  publication-title: Hum Mutat
  doi: 10.1002/humu.9389
– volume: 141
  start-page: 1404
  year: 2014
  end-page: 1415
  ident: CR13
  article-title: Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration
  publication-title: Development
  doi: 10.1242/dev.093526
– volume: 37
  start-page: 591
  year: 1995
  end-page: 605
  ident: CR1
  article-title: Intracranial cavernous malformations: lesion behavior and management strategies
  publication-title: Neurosurgery
  doi: 10.1227/00006123-199510000-00001
– volume: 285
  start-page: 11760
  year: 2010
  end-page: 11764
  ident: CR14
  article-title: Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotype
  publication-title: J Biol Chem
  doi: 10.1074/jbc.C109.097220
– volume: 286
  start-page: 25056
  year: 2011
  end-page: 25064
  ident: CR22
  article-title: CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M110.213777
– volume: 23
  start-page: 1066
  year: 2009
  end-page: 1072
  ident: CR33
  article-title: Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations
  publication-title: J Eur Acad Dermatol Venereol
  doi: 10.1111/j.1468-3083.2009.03263.x
– volume: 40
  start-page: 1659
  year: 2009
  end-page: 1665
  ident: CR38
  article-title: Immune response in human cerebral cavernous malformations
  publication-title: Stroke
  doi: 10.1161/STROKEAHA.108.538769
– volume: 30
  start-page: E24
  year: 2011
  ident: CR23
  article-title: The natural history of intracranial cavernous malformations
  publication-title: Neurosurg Focus
  doi: 10.3171/2011.3.FOCUS1165
– volume: 510
  start-page: 147
  year: 2011
  end-page: 159
  ident: CR27
  article-title: The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1δ
  publication-title: Arch Biochem Biophys
  doi: 10.1016/j.abb.2011.01.018
– volume: 362
  start-page: 121
  year: 2012
  end-page: 131
  ident: CR19
  article-title: Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease
  publication-title: Dev Biol
  doi: 10.1016/j.ydbio.2011.12.006
– volume: 21
  start-page: 215
  year: 2011
  end-page: 224
  ident: CR10
  article-title: Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation
  publication-title: Brain Pathol
  doi: 10.1111/j.1750-3639.2010.00441.x
– volume: 57
  start-page: 1825
  year: 2001
  end-page: 1828
  ident: CR24
  article-title: Prospective follow-up of 33 asymptomatic patients with familial cerebral cavernous malformations
  publication-title: Neurology
  doi: 10.1212/WNL.57.10.1825
– volume: 121
  start-page: 1871
  year: 2011
  end-page: 1881
  ident: CR16
  article-title: Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice
  publication-title: J Clin Invest
  doi: 10.1172/JCI44393
– volume: 59
  start-page: 1278
  year: 2006
  end-page: 84; discussion 1284
  ident: CR9
  article-title: Spectrum of genotype and clinical manifestations in cerebral cavernous malformations
  publication-title: Neurosurgery
  doi: 10.1227/01.NEU.0000249188.38409.03
– volume: 80
  start-page: 422
  year: 1994
  end-page: 432
  ident: CR25
  article-title: The natural history of familial cavernous malformations: results of an ongoing study
  publication-title: J Neurosurg
  doi: 10.3171/jns.1994.80.3.0422
– volume: 207
  start-page: 881
  year: 2010
  end-page: 896
  ident: CR15
  article-title: Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity
  publication-title: J Exp Med
  doi: 10.1084/jem.20091258
– volume: 579
  start-page: 6611
  year: 2005
  end-page: 6615
  ident: CR28
  article-title: Phosphorylation of Thr695 and Thr850 on the myosin phosphatase target subunit: inhibitory effects and occurrence in A7r5 cells
  publication-title: FEBS Lett
  doi: 10.1016/j.febslet.2005.10.055
– volume: 18
  start-page: 919
  year: 2009
  end-page: 930
  ident: CR31
  article-title: Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddn430
– volume: 11
  start-page: 217
  year: 2012
  end-page: 224
  ident: CR7
  article-title: Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study
  publication-title: Lancet Neurol
  doi: 10.1016/S1474-4422(12)70004-2
– volume: 123
  start-page: 1274
  issue: Pt 8
  year: 2010
  end-page: 1284
  ident: CR17
  article-title: CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation
  publication-title: J Cell Sci
  doi: 10.1242/jcs.061341
– volume: 498
  start-page: 492
  year: 2013
  end-page: 496
  ident: CR4
  article-title: EndMT contributes to the onset and progression of cerebral cavernous malformations
  publication-title: Nature
  doi: 10.1038/nature12207
– volume: 36
  start-page: 872
  year: 2005
  end-page: 874
  ident: CR30
  article-title: Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion
  publication-title: Stroke
  doi: 10.1161/01.STR.0000157586.20479.fd
– volume: 43
  start-page: 571
  year: 2012
  end-page: 574
  ident: CR3
  article-title: Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease
  publication-title: Stroke
  doi: 10.1161/STROKEAHA.111.625467
– volume: 27
  start-page: 141
  year: 2013
  end-page: 146
  ident: CR6
  article-title: Cavernous malformations and hemorrhage risk
  publication-title: Prog Neurol Surg
  doi: 10.1159/000341774
– volume: 17
  start-page: 407
  year: 2013
  end-page: 418
  ident: CR18
  article-title: Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations
  publication-title: J Cell Mol Med
  doi: 10.1111/jcmm.12022
– volume: 20
  start-page: 211
  year: 2011
  end-page: 222
  ident: CR21
  article-title: A novel mouse model of cerebral cavernous malformations based on the two-hit mutation hypothesis recapitulates the human disease
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddq433
– volume: 74
  start-page: 818
  year: 2010
  end-page: 826
  ident: CR35
  article-title: Pleiotropic effects of statins. - Basic research and clinical perspectives -
  publication-title: Circ J
  doi: 10.1253/circj.CJ-10-0110
– volume: 83
  start-page: 7
  year: 2013
  end-page: 14
  ident: CR40
  article-title: Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management
  publication-title: Clin Genet
  doi: 10.1111/j.1399-0004.2012.01892.x
– volume: 76
  start-page: 42
  year: 2005
  end-page: 51
  ident: CR2
  article-title: Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations
  publication-title: Am J Hum Genet
  doi: 10.1086/426952
– ident: 10.1038/gim.2014.97_bb0070
– ident: 10.1038/gim.2014.97_bb0100
– ident: 10.1038/gim.2014.97_bb0135
– ident: 10.1038/gim.2014.97_bb0150
– ident: 10.1038/gim.2014.97_bb0025
– ident: 10.1038/gim.2014.97_bb0140
– ident: 10.1038/gim.2014.97_bb0195
– ident: 10.1038/gim.2014.97_bb0045
– ident: 10.1038/gim.2014.97_bb0095
– ident: 10.1038/gim.2014.97_bb0040
– ident: 10.1038/gim.2014.97_bb0145
– ident: 10.1038/gim.2014.97_bb0080
– ident: 10.1038/gim.2014.97_bb0115
– ident: 10.1038/gim.2014.97_bb0165
– ident: 10.1038/gim.2014.97_bb0185
– ident: 10.1038/gim.2014.97_bb0055
– ident: 10.1038/gim.2014.97_bb0090
– ident: 10.1038/gim.2014.97_bb0010
– ident: 10.1038/gim.2014.97_bb0160
– ident: 10.1038/gim.2014.97_bb0190
– ident: 10.1038/gim.2014.97_bb0105
– ident: 10.1038/gim.2014.97_bb0175
– ident: 10.1038/gim.2014.97_bb0035
– ident: 10.1038/gim.2014.97_bb0060
– ident: 10.1038/gim.2014.97_bb0110
– ident: 10.1038/gim.2014.97_bb0020
– ident: 10.1038/gim.2014.97_bb0170
– ident: 10.1038/gim.2014.97_bb0155
– ident: 10.1038/gim.2014.97_bb0015
– ident: 10.1038/gim.2014.97_bb0205
– ident: 10.1038/gim.2014.97_bb0065
– ident: 10.1038/gim.2014.97_bb0125
– ident: 10.1038/gim.2014.97_bb0075
– ident: 10.1038/gim.2014.97_bb0030
– ident: 10.1038/gim.2014.97_bb0050
– ident: 10.1038/gim.2014.97_bb0120
– ident: 10.1038/gim.2014.97_bb0180
– ident: 10.1038/gim.2014.97_bb0200
– ident: 10.1038/gim.2014.97_bb0130
– ident: 10.1038/gim.2014.97_bb0085
SSID ssj0017320
Score 2.4718838
Snippet Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a...
The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a...
Purpose:The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a...
Purpose: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 188
SubjectTerms 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
631/208/737
692/420/2489/144
692/699/375/1370
Adolescent
Adult
Animals
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Biomedicine
Carrier Proteins - genetics
Cells, Cultured
Central Nervous System Neoplasms - enzymology
Central Nervous System Neoplasms - genetics
Central Nervous System Neoplasms - pathology
Child
Child, Preschool
Disease Models, Animal
Hemangioma, Cavernous, Central Nervous System - enzymology
Hemangioma, Cavernous, Central Nervous System - genetics
Hemangioma, Cavernous, Central Nervous System - pathology
Human Genetics
Human Umbilical Vein Endothelial Cells
Humans
Infant
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Keratin-1 - genetics
Laboratory Medicine
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Middle Aged
Mutation
original-research-article
Prospective Studies
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
Stress Fibers - drug effects
Stress Fibers - metabolism
Young Adult
Title Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations
URI https://link.springer.com/article/10.1038/gim.2014.97
https://www.ncbi.nlm.nih.gov/pubmed/25122144
https://www.proquest.com/docview/1844715517
https://www.proquest.com/docview/1660926504
https://www.proquest.com/docview/1680460457
https://pubmed.ncbi.nlm.nih.gov/PMC4329119
Volume 17
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3dSxwxEB9apaUv0tqvVSsp2JdC2t1Nstk8lVZPpKBIqXBvSzabtMK5Z7070P_emd3cVnvF5wxLspPMR36Z3wDsKaeV1qHkpaktl6opuEmt4-iNmkJqJ0QgRPf4pDg6k9_Hahwv3GbxWeXSJnaGupk6uiP_jJkI2lH07_rL5R9OXaMIXY0tNB7DOlGXUfKlx0PClWmR92wEpuQCPXusz0sFJn3nVIaeyU_E9nTXI62EmauvJf-BTDtPdPgcNmIIyb72On8Bj3y7CU_6ppI3m_D0OMLlLyGMruOrFZS3v7rUOlo3Ng3M-SuCjSfMWWq4O13M2IWdDOWMLII3zEYV-obRtS07Pdg_yFJ2sehh_NkrODsc_dw_4rGxAndSmznPlTOm1gWVkdIB99KkdSNrVVuXe43mLw3KW_T-oUbXpkKW4pi0WaG9ckGI17DWTlv_FpjMM2tc0wRRBqI2tL7MlPe-dsHrRtkEPi5_buUi6zg1v5hUHfotygo1UZEmKqMT2BuEL3uyjf-L7Sy1VMUTN6v-7o8E3g_DeFYIALGtx39YZUWRmhxjUvmQTElYsVT4nTe94oe5UCxIFHMJ6HtbYhAgru77I-35746zW4oc3YpJ4MNy89yZ-uoStx5e4jY8Q0HVv4XbgbX51cK_w-BoXu92J2AX1r-NTk5_3AKOUBGM
linkProvider ProQuest
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB5VRUAvCMqjgQJGai9IgTzsOD4ghLqttrRbcWilvQXHsaHSNlu6u4L-KX4jM4kTWhb11rMnUeJ5-xvPAGwJI4WULg9zVeqQiyoLVaRNiN6oyrg0aeoI0R0dZcMT_nksxivwu7sLQ2WVnU1sDHU1NXRG_h4zEbSj6N_lx_MfIU2NInS1G6HRisWBvfyJKdvsw_4A-budJHu7xzvD0E8VCA2Xah4mwihVYvae8ka6LVdRWfFSlNokVqLuR05Yja7PlWjXhYsjXOM6zqQVxtEBKJr8O-h4IyohlOM-wYtlmrTdD1QephhJ-PuAUYpJ5ilde4_5O-ouddUDLoW1y9WZ_0C0jefbewgPfMjKPrUy9ghWbL0Od9shlpfrcG_k4fnH4HZ_-SoZpNffmlTeW1M2dczYC4KpJ8xoGvA7XczYmZ701yeZB4uY9iJjK0bHxOzLYGcQR-xs0ZYNzJ7Aya1s-VNYrae13QDGk1grU1UuzR21UtQ2j4W1tjTOykroAN52m1sY3-Wchm1MigZtT_MCOVEQJwolA9jqic_b5h7_J9vsuFR4DZ8Vf-UxgDf9MuomAS66triHRZxlkUowBuY30eSETXOB73nWMr7_Foo9qaVdAPKaSPQE1Bv8-kp9-r3pEc7TBN2YCmC7E54rn778i89v_sXXcH94PDosDvePDl7AGj4k2jq8TVidXyzsSwzM5uWrRhsYfL1t9fsDhMBLlw
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB5VRVRcEJRXoICR2gtSaBLbcXxACHW7aimteqDS3oLj2FBpu1u6u4L-NX4dM4kTWhb11rMnUeJ5-xvPAGxKq6RSvogLXZlYyDqPdWJsjN6ozoWynHtCdA-P8r0T8WkkRyvwu7sLQ2WVnU1sDHU9tXRGvo2ZCNpR9O9q24eyiOPB8MP5j5gmSBHS2o3TaEXkwF3-xPRt9n5_gLzeyrLh7pedvThMGIitUHoeZ9JqXWEmz0Uj6U7opKpFJStjM6fQDiReOoNu0Fdo46VPE1wTJs2Vk9bTYSia_zuKo9tEXVKjPtlLFc_aTgi6iDlGFeFuYMIx4TylK_CpeEedpq56w6UQd7lS8x-4tvGCwwdwP4Sv7GMrbw9hxU3W4W470PJyHdYOA1T_CPzur1Axg_TmW5PWB8vKpp5Zd0GQ9ZhZQ8N-p4sZOzPj_iolC8ARM0F8XM3oyJgdD3YGacLOFm0JwewxnNzKlj-B1cl04p4BE1lqtK1rzwtPbRWNK1LpnKusd6qWJoK33eaWNnQ8p8Eb47JB3nlRIidK4kSpVQSbPfF52-jj_2QbHZfKoO2z8q9sRvCmX0Y9JfDFTBzuYZnmeaIzjIfFTTQF4dRC4nuetozvv4XiUGpvF4G6JhI9AfUJv74yOf3e9AsXPEOXpiPY6oTnyqcv_-Lzm3_xNayh4pWf948OXsA9fEa2JXkbsDq_WLiXGKPNq1eNMjD4etva9wffWE_N
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Exceptional+aggressiveness+of+cerebral+cavernous+malformation+disease+associated+with+PDCD10+mutations&rft.jtitle=Genetics+in+medicine&rft.au=Shenkar%2C+Robert&rft.au=Shi%2C+Changbin&rft.au=Rebeiz%2C+Tania&rft.au=Stockton%2C+Rebecca+A&rft.date=2015-03-01&rft.pub=Elsevier+Limited&rft.issn=1098-3600&rft.eissn=1530-0366&rft.volume=17&rft.issue=3&rft.spage=188&rft_id=info:doi/10.1038%2Fgim.2014.97&rft.externalDBID=HAS_PDF_LINK&rft.externalDocID=4265482841
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1098-3600&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1098-3600&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1098-3600&client=summon