NPHP4 Variants Are Associated With Pleiotropic Heart Malformations
RATIONALE:Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. OBJECTIVE:To identify genetic mut...
Saved in:
| Published in | Circulation research Vol. 110; no. 12; pp. 1564 - 1574 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
American Heart Association, Inc
08.06.2012
Lippincott Williams & Wilkins |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-7330 1524-4571 1524-4571 |
| DOI | 10.1161/CIRCRESAHA.112.269795 |
Cover
Loading…
| Abstract | RATIONALE:Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs.
OBJECTIVE:To identify genetic mutations causing cardiac laterality defects.
METHODS AND RESULTS:We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupfferʼs vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry.
CONCLUSIONS:NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupfferʼs vesicle cilia and is required for global L-R patterning. |
|---|---|
| AbstractList | RATIONALE:Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs.
OBJECTIVE:To identify genetic mutations causing cardiac laterality defects.
METHODS AND RESULTS:We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupfferʼs vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry.
CONCLUSIONS:NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupfferʼs vesicle cilia and is required for global L-R patterning. Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs.RATIONALECongenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs.To identify genetic mutations causing cardiac laterality defects.OBJECTIVETo identify genetic mutations causing cardiac laterality defects.We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry.METHODS AND RESULTSWe performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry.NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning.CONCLUSIONSNPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning. Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. To identify genetic mutations causing cardiac laterality defects. We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry. NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning. |
| Author | Jadot, Elodie Belmont, John W. van de Laar, Ingrid M.B.H. Jiang, Zhengxin Bertoli-Avella, Aida M. Roos-Hesselink, Jolien W. Oostra, Ben A. Wessels, Marja W. Swagemakers, Sigrid French, Vanessa M. van Tienhoven, Marianne Venselaar, Hanka Wang, Guangliang Meijers-Heijboer, Hanne Frohn-Mulder, Ingrid M.E. Severijnen, Lies-Anne Rohe, Christan Schot, Rachel Amack, Jeffrey D. Verkerk, Annemieke Mientjes, Edwin Najmabadi, Hossein Helbing, Wim A. de Graaf, Bianca M. Rahimi, Zohreh Devriendt, Koen Breedveld, Guido Willemsen, Rob de Graaff, Esther |
| AuthorAffiliation | From the Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (V.M.F., I.M.B.H.v.d.L., M.W.W., C.R., L.-A.S., B.M.d.G., R.S., G.B., E.M., M.v.T., R.W., B.A.O., A.M.B.-A.); the Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands (J.W.R.-H.); State University of New York, Upstate Medical University, Department of Cell and Developmental Biology, Syracuse, NY (G.W., J.D.A.); the Department of Pediatric Cardiology, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands (I.M.E.F.-M., W.A.H.); Lille University of Sciences and Technologies, Lille, France (E.J.); the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX (Z.J., J.W.B.); the Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands (A.V., S.S.); the Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (S.S.); Center for Molecular and Biomolecular Informatics (CMBI) and Nijmegen Center for Molecular |
| AuthorAffiliation_xml | – name: From the Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (V.M.F., I.M.B.H.v.d.L., M.W.W., C.R., L.-A.S., B.M.d.G., R.S., G.B., E.M., M.v.T., R.W., B.A.O., A.M.B.-A.); the Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands (J.W.R.-H.); State University of New York, Upstate Medical University, Department of Cell and Developmental Biology, Syracuse, NY (G.W., J.D.A.); the Department of Pediatric Cardiology, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands (I.M.E.F.-M., W.A.H.); Lille University of Sciences and Technologies, Lille, France (E.J.); the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX (Z.J., J.W.B.); the Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands (A.V., S.S.); the Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (S.S.); Center for Molecular and Biomolecular Informatics (CMBI) and Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Center, The Netherlands (H.V.); Medical Biology Research Center and Biochemistry Department, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran (Z.R.).; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (H.N.); the Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands (H.M.-H.); the Department of Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands (E.d.G.); and the Department of Clinical Genetics, University Hospital Leuven, Leuven, Belgium (K.D.) – name: 4 Department of Pediatric Cardiology, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands – name: 8 Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands – name: 12 Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands – name: 5 Lille University of Sciences and Technologies, Lille, France – name: 6 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States – name: 10 Medical Biology Research Center and Biochemistry Department, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran – name: 2 Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands – name: 7 Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands – name: 13 Department of Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands – name: 14 Department of Clinical Genetics, University Hospital Leuven, Leuven, Belgium – name: 9 Center for Molecular and Biomolecular Informatics (CMBI) and Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Center, The Netherlands – name: 3 State University of New York Upstate Medical University, Department of Cell and Developmental Biology, Syracuse, New York, United States – name: 1 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands – name: 11 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran |
| Author_xml | – sequence: 1 givenname: Vanessa surname: French middlename: M. fullname: French, Vanessa M. organization: From the Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (V.M.F., I.M.B.H.v.d.L., M.W.W., C.R., L.-A.S., B.M.d.G., R.S., G.B., E.M., M.v.T., R.W., B.A.O., A.M.B.-A.); the Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands (J.W.R.-H.); State University of New York, Upstate Medical University, Department of Cell and Developmental Biology, Syracuse, NY (G.W., J.D.A.); the Department of Pediatric Cardiology, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands (I.M.E.F.-M., W.A.H.); Lille University of Sciences and Technologies, Lille, France (E.J.); the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX (Z.J., J.W.B.); the Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands (A.V., S.S.); the Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (S.S.); Center for Molecular and Biomolecular Informatics (CMBI) and Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Center, The Netherlands (H.V.); Medical Biology Research Center and Biochemistry Department, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran (Z.R.).; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (H.N.); the Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands (H.M.-H.); the Department of Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands (E.d.G.); and the Department of Clinical Genetics, University Hospital Leuven, Leuven, Belgium (K.D.) – sequence: 2 givenname: Ingrid surname: van de Laar middlename: M.B.H. fullname: van de Laar, Ingrid M.B.H. – sequence: 3 givenname: Marja surname: Wessels middlename: W. fullname: Wessels, Marja W. – sequence: 4 givenname: Christan surname: Rohe fullname: Rohe, Christan – sequence: 5 givenname: Jolien surname: Roos-Hesselink middlename: W. fullname: Roos-Hesselink, Jolien W. – sequence: 6 givenname: Guangliang surname: Wang fullname: Wang, Guangliang – sequence: 7 givenname: Ingrid surname: Frohn-Mulder middlename: M.E. fullname: Frohn-Mulder, Ingrid M.E. – sequence: 8 givenname: Lies-Anne surname: Severijnen fullname: Severijnen, Lies-Anne – sequence: 9 givenname: Bianca surname: de Graaf middlename: M. fullname: de Graaf, Bianca M. – sequence: 10 givenname: Rachel surname: Schot fullname: Schot, Rachel – sequence: 11 givenname: Guido surname: Breedveld fullname: Breedveld, Guido – sequence: 12 givenname: Edwin surname: Mientjes fullname: Mientjes, Edwin – sequence: 13 givenname: Marianne surname: van Tienhoven fullname: van Tienhoven, Marianne – sequence: 14 givenname: Elodie surname: Jadot fullname: Jadot, Elodie – sequence: 15 givenname: Zhengxin surname: Jiang fullname: Jiang, Zhengxin – sequence: 16 givenname: Annemieke surname: Verkerk fullname: Verkerk, Annemieke – sequence: 17 givenname: Sigrid surname: Swagemakers fullname: Swagemakers, Sigrid – sequence: 18 givenname: Hanka surname: Venselaar fullname: Venselaar, Hanka – sequence: 19 givenname: Zohreh surname: Rahimi fullname: Rahimi, Zohreh – sequence: 20 givenname: Hossein surname: Najmabadi fullname: Najmabadi, Hossein – sequence: 21 givenname: Hanne surname: Meijers-Heijboer fullname: Meijers-Heijboer, Hanne – sequence: 22 givenname: Esther surname: de Graaff fullname: de Graaff, Esther – sequence: 23 givenname: Wim surname: Helbing middlename: A. fullname: Helbing, Wim A. – sequence: 24 givenname: Rob surname: Willemsen fullname: Willemsen, Rob – sequence: 25 givenname: Koen surname: Devriendt fullname: Devriendt, Koen – sequence: 26 givenname: John surname: Belmont middlename: W. fullname: Belmont, John W. – sequence: 27 givenname: Ben surname: Oostra middlename: A. fullname: Oostra, Ben A. – sequence: 28 givenname: Jeffrey surname: Amack middlename: D. fullname: Amack, Jeffrey D. – sequence: 29 givenname: Aida surname: Bertoli-Avella middlename: M. fullname: Bertoli-Avella, Aida M. |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25967749$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22550138$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFkktvEzEUhS3UiqaFnwCaDRKbKX57LCSkEBVSqUBUXkvrxuMhBmccbIeKf49L0hbYsLF17e-cK5_rY3QwxtEh9IjgU0IkeTY7v5xdnr2fzqe1pqdUaqXFPTQhgvKWC0UO0ARjrFvFGD5Cxzl_xZhwRvV9dESpEJiwboJevl3MF7z5BMnDWHIzTa6Z5hyth-L65rMvq2YRnI8lxY23zdxBKs0bCENMayg-jvkBOhwgZPdwv5-gj6_OPszm7cW71-ez6UVreSdVyzUWjPIOxKAch06yXhOsqBuk7VynJXUWQAgY2HLJmHKkp0B6QqHvQWrBTtCLne9mu1y73rqxJAhmk_wa0k8TwZu_b0a_Ml_iD8N0DYyQavB0b5Di963Lxax9ti4EGF3cZkMw0ZKwml1FH__Z67bJTXAVeLIHINuaRoLR-nzHCS2V4rpyYsfZFHNObrhFCDbXgzR3g6w1NbtBVt3zf3TWl99516f58F8136mvYigu5W9he-WSWTkIZWXqt8AME9rSumCJO9xeHyn2C2RJsyw |
| CODEN | CIRUAL |
| CitedBy_id | crossref_primary_10_1002_ajmg_c_31828 crossref_primary_10_1038_s41598_018_30204_3 crossref_primary_10_1016_j_lpm_2017_05_014 crossref_primary_10_1371_journal_pone_0191605 crossref_primary_10_1007_s00018_013_1430_1 crossref_primary_10_1161_CIRCRESAHA_121_320624 crossref_primary_10_1002_ajmg_a_37108 crossref_primary_10_1242_dmm_049568 crossref_primary_10_1186_2046_2530_1_23 crossref_primary_10_1542_neo_16_6_e340 crossref_primary_10_1371_journal_pgen_1007142 crossref_primary_10_1016_j_mod_2020_103611 crossref_primary_10_1016_j_gde_2013_05_004 crossref_primary_10_1038_s41569_021_00635_z crossref_primary_10_1038_s41401_024_01392_8 crossref_primary_10_3390_genes13071214 crossref_primary_10_1161_JAHA_122_028226 crossref_primary_10_1016_j_jgg_2024_07_014 crossref_primary_10_1161_CIRCRESAHA_116_309140 crossref_primary_10_1016_j_tcm_2014_11_007 crossref_primary_10_1534_g3_115_019943 crossref_primary_10_1017_erm_2014_22 crossref_primary_10_1371_journal_pgen_1010530 crossref_primary_10_3389_fped_2018_00183 crossref_primary_10_4161_org_27483 crossref_primary_10_1161_CIRCRESAHA_120_316778 crossref_primary_10_3390_cells7120233 crossref_primary_10_1016_j_trsl_2013_10_007 crossref_primary_10_1007_s00380_021_01953_5 crossref_primary_10_1097_CM9_0000000000003192 |
| Cites_doi | 10.1242/dev.02595 10.1681/ASN.2008050456 10.1038/nature07520 10.1086/344395 10.1002/humu.9326 10.1093/hmg/ddr164 10.1038/nrm2278 10.1016/j.cell.2006.09.018 10.1681/ASN.2006101164 10.1242/jcs.037408 10.1242/dev.01772 10.1093/hmg/ddr214 10.1126/science.1063525 10.1002/ajmg.c.30231 10.1002/cm.20428 10.1681/ASN.2006121344 10.1016/j.ajhg.2008.02.017 10.1242/dev.00436 10.1146/annurev.genom.4.070802.110428 10.1016/S0092-8674(00)81705-5 10.1038/ki.2011.284 10.1038/ng1217 10.1152/ajprenal.00043.2010 10.1097/00001573-200405000-00005 10.1038/ng1216 10.1007/s00439-007-0436-x 10.1002/ajmg.c.30228 10.1016/j.cell.2011.04.019 10.1038/ng996 10.1016/j.ajhg.2008.05.012 10.1093/hmg/3.2.331 10.1002/dvdy.22355 10.1038/40140 10.1242/dev.01663 10.1159/000320888 10.1681/ASN.2007020243 10.1136/jmg.38.3.182 10.1136/hrt.2009.181685 10.1017/S1047951107001138 10.1002/humu.21337 10.1016/S0092-8674(03)00511-7 10.1038/nature03494 10.1093/hmg/ddn411 10.1086/341031 10.1161/circulationaha.106.649038 10.1038/sj.ejhg.5201506 10.1038/ng1197-305 |
| ContentType | Journal Article |
| Copyright | 2012 American Heart Association, Inc. 2015 INIST-CNRS |
| Copyright_xml | – notice: 2012 American Heart Association, Inc. – notice: 2015 INIST-CNRS |
| DBID | AAYXX CITATION IQODW CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1161/CIRCRESAHA.112.269795 |
| DatabaseName | CrossRef Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| 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 |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1524-4571 |
| EndPage | 1574 |
| ExternalDocumentID | PMC3916111 22550138 25967749 10_1161_CIRCRESAHA_112_269795 00003012-201206080-00007 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: R01HL095690 – fundername: NHLBI NIH HHS grantid: R01 HL095690 – fundername: National Heart, Lung, and Blood Institute : NHLBI grantid: R01 HL095690 || HL |
| GroupedDBID | --- -~X .-D .3C .Z2 01R 0R~ 18M 1J1 29B 2WC 40H 4Q1 4Q2 4Q3 53G 5GY 5RE 5VS 71W 77Y 7O~ AAAAV AAAXR AAGIX AAHPQ AAIQE AAMOA AAMTA AARTV AASOK AAXQO ABBUW ABDIG ABJNI ABOCM ABPXF ABQRW ABXVJ ABZAD ACCJW ACDDN ACEWG ACGFO ACGFS ACILI ACNWC ACPRK ACWDW ACWRI ACXNZ ACZKN ADBBV ADGGA ADHPY ADNKB AE3 AE6 AEETU AENEX AFDTB AFUWQ AGINI AHMBA AHOMT AHQNM AHVBC AIJEX AINUH AJCLO AJIOK AJNWD AJNYG AJZMW ALKUP ALMA_UNASSIGNED_HOLDINGS AMJPA AMNEI BAWUL BOYCO BQLVK BYPQX C45 CS3 DIK DIWNM DU5 DUNZO E.X E3Z EBS EJD EX3 F2K F2L F2M F2N F5P FCALG FL- FRP FW0 GX1 H0~ H13 HZ~ IKREB IKYAY IN~ JK3 JK8 K8S KD2 KMI KQ8 L-C L7B N9A N~7 N~B O9- OAG OAH OB2 OK1 OL1 OLG OLH OLU OLV OLY OLZ OPUJH OUVQU OVD OVDNE OVIDH OVLEI OWW OWY OXXIT P2P PQQKQ RAH RLZ S4R S4S T8P TEORI TR2 UPT V2I VVN W3M W8F WH7 WOQ WOW X3V X3W YFH YOC ZFV ZZMQN AAYXX ADGHP CITATION .55 .GJ 1CY 41~ AAQKA AASCR ABASU ABVCZ ABZZY ACLDA ACXJB ADFPA AFBFQ AFFNX AHRYX AKCTQ AKULP ALMTX AMKUR AOHHW AOQMC BS7 C1A EEVPB ERAAH GNXGY GQDEL HLJTE H~9 IPNFZ IQODW J5H JF9 JG8 MVM N~M OCUKA ODA ORVUJ OWU OWV OWX OWZ P-K R58 RIG TSPGW X7M XXN XYM ZGI ACIJW CGR CUY CVF ECM EIF NPM 7X8 5PM |
| ID | FETCH-LOGICAL-c4867-49053248a5f7e4a863d91072ef6c8e8962ecaa55af3bb337e1d2a1d12adda6953 |
| ISSN | 0009-7330 1524-4571 |
| IngestDate | Thu Aug 21 13:54:23 EDT 2025 Fri Jul 11 06:32:35 EDT 2025 Thu Apr 03 06:58:26 EDT 2025 Mon Jul 21 09:12:45 EDT 2025 Thu Apr 24 23:08:16 EDT 2025 Tue Jul 01 01:24:44 EDT 2025 Fri May 16 03:47:18 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 12 |
| Keywords | Heart Congenital nphp4 congenital heart malformations Vertebrata Brachydanio rerio Mammalia Malformation Pisces heterotaxy cilia Circulatory system zebrafish |
| Language | English |
| License | CC BY 4.0 |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c4867-49053248a5f7e4a863d91072ef6c8e8962ecaa55af3bb337e1d2a1d12adda6953 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally |
| OpenAccessLink | https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.112.269795 |
| PMID | 22550138 |
| PQID | 1019613571 |
| PQPubID | 23479 |
| PageCount | 11 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_3916111 proquest_miscellaneous_1019613571 pubmed_primary_22550138 pascalfrancis_primary_25967749 crossref_primary_10_1161_CIRCRESAHA_112_269795 crossref_citationtrail_10_1161_CIRCRESAHA_112_269795 wolterskluwer_health_00003012-201206080-00007 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2012-June-8 |
| PublicationDateYYYYMMDD | 2012-06-08 |
| PublicationDate_xml | – month: 06 year: 2012 text: 2012-June-8 day: 08 |
| PublicationDecade | 2010 |
| PublicationPlace | Hagerstown, MD |
| PublicationPlace_xml | – name: Hagerstown, MD – name: United States |
| PublicationTitle | Circulation research |
| PublicationTitleAlternate | Circ Res |
| PublicationYear | 2012 |
| Publisher | American Heart Association, Inc Lippincott Williams & Wilkins |
| Publisher_xml | – name: American Heart Association, Inc – name: Lippincott Williams & Wilkins |
| References | e_1_3_5_25_2 e_1_3_5_23_2 e_1_3_5_21_2 Shiba D (e_1_3_5_27_2) 2010; 67 e_1_3_5_44_2 e_1_3_5_46_2 e_1_3_5_48_2 e_1_3_5_29_2 e_1_3_5_40_2 Otto EA (e_1_3_5_22_2) 2010; 10 e_1_3_5_42_2 e_1_3_5_7_2 e_1_3_5_9_2 e_1_3_5_3_2 e_1_3_5_5_2 e_1_3_5_39_2 e_1_3_5_16_2 e_1_3_5_37_2 e_1_3_5_14_2 e_1_3_5_12_2 e_1_3_5_35_2 e_1_3_5_10_2 Shiba D (e_1_3_5_28_2) 2011; 12 e_1_3_5_33_2 e_1_3_5_18_2 e_1_3_5_50_2 e_1_3_5_31_2 e_1_3_5_26_2 e_1_3_5_24_2 e_1_3_5_43_2 e_1_3_5_45_2 e_1_3_5_47_2 e_1_3_5_49_2 e_1_3_5_2_2 e_1_3_5_41_2 e_1_3_5_8_2 e_1_3_5_20_2 e_1_3_5_4_2 e_1_3_5_6_2 e_1_3_5_17_2 e_1_3_5_38_2 e_1_3_5_15_2 e_1_3_5_36_2 e_1_3_5_13_2 e_1_3_5_34_2 e_1_3_5_11_2 e_1_3_5_32_2 e_1_3_5_19_2 e_1_3_5_30_2 12702646 - Development. 2003 Jun;130(11):2303-16 15716348 - Development. 2005 Mar;132(6):1247-60 22169048 - Differentiation. 2012 Feb;83(2):S91-6 19933292 - Heart. 2010 May;96(9):673-7 12244321 - Nat Genet. 2002 Oct;32(2):300-5 15790966 - Development. 2005 Apr;132(8):1907-21 12872123 - Nat Genet. 2003 Aug;34(4):413-20 15889083 - Nature. 2005 May 12;435(7039):172-7 20169535 - Cytoskeleton (Hoboken). 2010 Feb;67(2):112-9 12730129 - Annu Rev Genomics Hum Genet. 2003;4:1-32 12016587 - Am J Hum Genet. 2002 Jul;71(1):22-9 20690115 - Hum Mutat. 2010 Oct;31(10):1097-108 21596840 - Hum Mol Genet. 2011 Aug 15;20(16):3119-28 12859898 - Cell. 2003 Jul 11;114(1):61-73 17515466 - Circulation. 2007 Jun 5;115(22):2814-21 17938964 - Hum Genet. 2008 Jan;122(6):595-603 12872122 - Nat Genet. 2003 Aug;34(4):455-9 19043402 - Nature. 2009 Jan 8;457(7226):205-9 9865700 - Cell. 1998 Dec 11;95(6):829-37 19050042 - J Cell Sci. 2009 Jan 1;122(Pt 1):44-54 15096953 - Curr Opin Cardiol. 2004 May;19(3):216-20 17409309 - J Am Soc Nephrol. 2007 May;18(5):1566-75 18039396 - Cardiol Young. 2007 Sep;17 Suppl 2:1-28 21071979 - Nephron Exp Nephrol. 2011;118(1):e9-14 19876933 - Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):281-95 16251896 - Eur J Hum Genet. 2006 Jan;14(1):17-25 18538293 - Am J Hum Genet. 2008 Jul;83(1):18-29 11567139 - Science. 2001 Sep 21;293(5538):2256-9 17513324 - J Am Soc Nephrol. 2007 Jun;18(6):1855-71 17018270 - Cell. 2006 Oct 6;127(1):27-32 18371931 - Am J Hum Genet. 2008 Apr;82(4):959-70 17955020 - Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93 17855640 - J Am Soc Nephrol. 2007 Oct;18(10):2789-95 19118152 - J Am Soc Nephrol. 2009 Jan;20(1):23-35 19064609 - Hum Mol Genet. 2009 Mar 1;18(5):861-71 19876930 - Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):307-17 20568242 - Dev Dyn. 2010 Aug;239(8):2190-7 15776426 - Hum Mutat. 2005 Apr;25(4):411 21866095 - Kidney Int. 2011 Dec;80(11):1239-45 17021045 - Development. 2006 Nov;133(21):4131-43 20462968 - Am J Physiol Renal Physiol. 2010 Jul;299(1):F55-62 11303511 - J Med Genet. 2001 Mar;38(3):182-5 21068128 - J Med Genet. 2011 Feb;48(2):105-16 12205563 - Am J Hum Genet. 2002 Nov;71(5):1161-7 9354794 - Nat Genet. 1997 Nov;17(3):305-8 21498478 - Hum Mol Genet. 2011 Jul 1;20(13):2611-27 9353118 - Nature. 1997 Oct 30;389(6654):963-6 21565611 - Cell. 2011 May 13;145(4):513-28 8004104 - Hum Mol Genet. 1994 Feb;3(2):331-4 |
| References_xml | – ident: e_1_3_5_17_2 doi: 10.1242/dev.02595 – ident: e_1_3_5_19_2 doi: 10.1681/ASN.2008050456 – ident: e_1_3_5_34_2 doi: 10.1038/nature07520 – ident: e_1_3_5_39_2 doi: 10.1086/344395 – ident: e_1_3_5_31_2 doi: 10.1002/humu.9326 – ident: e_1_3_5_49_2 doi: 10.1093/hmg/ddr164 – ident: e_1_3_5_18_2 doi: 10.1038/nrm2278 – ident: e_1_3_5_37_2 doi: 10.1016/j.cell.2006.09.018 – ident: e_1_3_5_43_2 doi: 10.1681/ASN.2006101164 – ident: e_1_3_5_29_2 doi: 10.1242/jcs.037408 – ident: e_1_3_5_33_2 doi: 10.1242/dev.01772 – ident: e_1_3_5_32_2 doi: 10.1093/hmg/ddr214 – ident: e_1_3_5_44_2 doi: 10.1126/science.1063525 – ident: e_1_3_5_16_2 doi: 10.1002/ajmg.c.30231 – volume: 67 start-page: 112 year: 2010 ident: e_1_3_5_27_2 article-title: Inv acts as a molecular anchor for nphp3 and nek8 in the proximal segment of primary cilia publication-title: Cytoskeleton doi: 10.1002/cm.20428 – volume: 10 start-page: 10 year: 2010 ident: e_1_3_5_22_2 article-title: Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy publication-title: J Med Genet – ident: e_1_3_5_20_2 doi: 10.1681/ASN.2006121344 – ident: e_1_3_5_25_2 doi: 10.1016/j.ajhg.2008.02.017 – ident: e_1_3_5_36_2 doi: 10.1242/dev.00436 – ident: e_1_3_5_2_2 doi: 10.1146/annurev.genom.4.070802.110428 – ident: e_1_3_5_12_2 doi: 10.1016/S0092-8674(00)81705-5 – ident: e_1_3_5_23_2 doi: 10.1038/ki.2011.284 – ident: e_1_3_5_24_2 doi: 10.1038/ng1217 – ident: e_1_3_5_50_2 doi: 10.1152/ajprenal.00043.2010 – ident: e_1_3_5_5_2 doi: 10.1097/00001573-200405000-00005 – ident: e_1_3_5_40_2 doi: 10.1038/ng1216 – ident: e_1_3_5_8_2 doi: 10.1007/s00439-007-0436-x – ident: e_1_3_5_4_2 doi: 10.1002/ajmg.c.30228 – ident: e_1_3_5_26_2 doi: 10.1016/j.cell.2011.04.019 – ident: e_1_3_5_38_2 doi: 10.1038/ng996 – ident: e_1_3_5_46_2 doi: 10.1016/j.ajhg.2008.05.012 – ident: e_1_3_5_30_2 doi: 10.1093/hmg/3.2.331 – volume: 12 start-page: 12 year: 2011 ident: e_1_3_5_28_2 article-title: The ciliary transitional zone and nephrocystins publication-title: Differentiation – ident: e_1_3_5_35_2 doi: 10.1002/dvdy.22355 – ident: e_1_3_5_11_2 doi: 10.1038/40140 – ident: e_1_3_5_13_2 doi: 10.1242/dev.01663 – ident: e_1_3_5_21_2 doi: 10.1159/000320888 – ident: e_1_3_5_42_2 doi: 10.1681/ASN.2007020243 – ident: e_1_3_5_7_2 doi: 10.1136/jmg.38.3.182 – ident: e_1_3_5_48_2 doi: 10.1136/hrt.2009.181685 – ident: e_1_3_5_3_2 doi: 10.1017/S1047951107001138 – ident: e_1_3_5_41_2 doi: 10.1002/humu.21337 – ident: e_1_3_5_15_2 doi: 10.1016/S0092-8674(03)00511-7 – ident: e_1_3_5_14_2 doi: 10.1038/nature03494 – ident: e_1_3_5_47_2 doi: 10.1093/hmg/ddn411 – ident: e_1_3_5_45_2 doi: 10.1086/341031 – ident: e_1_3_5_10_2 doi: 10.1161/circulationaha.106.649038 – ident: e_1_3_5_9_2 doi: 10.1038/sj.ejhg.5201506 – ident: e_1_3_5_6_2 doi: 10.1038/ng1197-305 – reference: 11303511 - J Med Genet. 2001 Mar;38(3):182-5 – reference: 15790966 - Development. 2005 Apr;132(8):1907-21 – reference: 19064609 - Hum Mol Genet. 2009 Mar 1;18(5):861-71 – reference: 12016587 - Am J Hum Genet. 2002 Jul;71(1):22-9 – reference: 19050042 - J Cell Sci. 2009 Jan 1;122(Pt 1):44-54 – reference: 18538293 - Am J Hum Genet. 2008 Jul;83(1):18-29 – reference: 9353118 - Nature. 1997 Oct 30;389(6654):963-6 – reference: 18039396 - Cardiol Young. 2007 Sep;17 Suppl 2:1-28 – reference: 16251896 - Eur J Hum Genet. 2006 Jan;14(1):17-25 – reference: 17955020 - Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93 – reference: 21068128 - J Med Genet. 2011 Feb;48(2):105-16 – reference: 21498478 - Hum Mol Genet. 2011 Jul 1;20(13):2611-27 – reference: 15096953 - Curr Opin Cardiol. 2004 May;19(3):216-20 – reference: 22169048 - Differentiation. 2012 Feb;83(2):S91-6 – reference: 18371931 - Am J Hum Genet. 2008 Apr;82(4):959-70 – reference: 19043402 - Nature. 2009 Jan 8;457(7226):205-9 – reference: 12859898 - Cell. 2003 Jul 11;114(1):61-73 – reference: 12730129 - Annu Rev Genomics Hum Genet. 2003;4:1-32 – reference: 12872123 - Nat Genet. 2003 Aug;34(4):413-20 – reference: 21565611 - Cell. 2011 May 13;145(4):513-28 – reference: 19876933 - Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):281-95 – reference: 19876930 - Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):307-17 – reference: 20568242 - Dev Dyn. 2010 Aug;239(8):2190-7 – reference: 21071979 - Nephron Exp Nephrol. 2011;118(1):e9-14 – reference: 20462968 - Am J Physiol Renal Physiol. 2010 Jul;299(1):F55-62 – reference: 12244321 - Nat Genet. 2002 Oct;32(2):300-5 – reference: 20690115 - Hum Mutat. 2010 Oct;31(10):1097-108 – reference: 15716348 - Development. 2005 Mar;132(6):1247-60 – reference: 17018270 - Cell. 2006 Oct 6;127(1):27-32 – reference: 17513324 - J Am Soc Nephrol. 2007 Jun;18(6):1855-71 – reference: 17938964 - Hum Genet. 2008 Jan;122(6):595-603 – reference: 17515466 - Circulation. 2007 Jun 5;115(22):2814-21 – reference: 21596840 - Hum Mol Genet. 2011 Aug 15;20(16):3119-28 – reference: 15889083 - Nature. 2005 May 12;435(7039):172-7 – reference: 11567139 - Science. 2001 Sep 21;293(5538):2256-9 – reference: 17855640 - J Am Soc Nephrol. 2007 Oct;18(10):2789-95 – reference: 12205563 - Am J Hum Genet. 2002 Nov;71(5):1161-7 – reference: 12702646 - Development. 2003 Jun;130(11):2303-16 – reference: 17409309 - J Am Soc Nephrol. 2007 May;18(5):1566-75 – reference: 21866095 - Kidney Int. 2011 Dec;80(11):1239-45 – reference: 19933292 - Heart. 2010 May;96(9):673-7 – reference: 8004104 - Hum Mol Genet. 1994 Feb;3(2):331-4 – reference: 9865700 - Cell. 1998 Dec 11;95(6):829-37 – reference: 9354794 - Nat Genet. 1997 Nov;17(3):305-8 – reference: 20169535 - Cytoskeleton (Hoboken). 2010 Feb;67(2):112-9 – reference: 12872122 - Nat Genet. 2003 Aug;34(4):455-9 – reference: 15776426 - Hum Mutat. 2005 Apr;25(4):411 – reference: 17021045 - Development. 2006 Nov;133(21):4131-43 – reference: 19118152 - J Am Soc Nephrol. 2009 Jan;20(1):23-35 |
| SSID | ssj0014329 |
| Score | 2.2645173 |
| Snippet | RATIONALE:Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right... Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R)... |
| SourceID | pubmedcentral proquest pubmed pascalfrancis crossref wolterskluwer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 1564 |
| SubjectTerms | Amino Acid Sequence Animals Biological and medical sciences Cohort Studies Female Fundamental and applied biological sciences. Psychology Genetic Pleiotropy - genetics Genetic Variation - genetics Genome-Wide Association Study - methods Heart Defects, Congenital - diagnosis Heart Defects, Congenital - genetics Heart Defects, Congenital - pathology Humans Male Molecular Sequence Data Pedigree Proteins - genetics Vertebrates: cardiovascular system Zebrafish |
| Title | NPHP4 Variants Are Associated With Pleiotropic Heart Malformations |
| URI | https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00003012-201206080-00007 https://www.ncbi.nlm.nih.gov/pubmed/22550138 https://www.proquest.com/docview/1019613571 https://pubmed.ncbi.nlm.nih.gov/PMC3916111 |
| Volume | 110 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb5swFLaiTpomVdPuY5eKSXtDzoIBYx7bbFWyLVVU9faGDJg2WxaiXDRpz_vhOweMATXStr6gBMch4ft88LG_cw4h71k0YLkQLg1lGOBqVUKTDA5SeSLhWQIuAsY7T0746Nz_fBVc9Xq_W6ql7Sbpp792xpXcBVU4B7hilOx_IGu-FE7Aa8AXjoAwHP8J45PpaOo7F-DulmoWFHHVt7tWlU_nalZsVsVylmLI0WrjTOTcRCyu23PT4WyV6mJejs4BZNaKjzEosFyBuZBoHKUz6ddtGAGVKeerrLTa48X1apZB-1F_ZD5ziSnK52sdHfRNOpem6bS4UU2aA01WvQ6Bgg5OB6JjWyMaenqXRWlzynzqB1WRFWNvtY5VE4u1zCdmrmk9it2gquBz28xzNPPD8ekQaHo4OsRAqD7jUVgV7GxBv_xRYg9WK8A92eapZ7SI08kQg49dDBC_x8DZwDoYH8dfzF6U77GorseH_0_HgUGXDzt_AeaX1pfrTHb2l3IN4y6vCqbs8mhuC3P3fxYomlh_L2MmWjOfs0fkoXZZ7MOKf49JTy2ekPsTLcp4So5KGto1DW2god3Q0EYa2i0a2iUN7Q4Nn5Hz409nwxHVpTloiikaqR9hRRFfyCAPlS8F9zKYd4ZM5TwVSkScqVTKIJC5lySeFyo3Y9LNXAaPU8mjwHtO9hbFQr0kdipcz80HUvhCwdw-E5mbJlnu5UKFPAtSi_j1PYxTnbcey6fM49J_5W7coADvWVyhYJG-6basErf8rcNBByDTiwURBycpssi7GrEYbDBurMGIK7ZrlElGMC0GnlvkRYVg01tTwSJhB1vzAczv3m1ZzG7KPO-alhahHRbEVYQ0ykZwPYNRHI0DDq4fLYUJr-58pdfkQTOy35C9zWqr3sKce5MclEPiD0LD0Kg |
| linkProvider | Flying Publisher |
| 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=NPHP4+Variants+are+Associated+with+Pleiotropic+Heart+Malformations&rft.jtitle=Circulation+research&rft.au=French%2C+Vanessa+M.&rft.au=van+de+Laar%2C+Ingrid+M.B.H.&rft.au=Wessels%2C+Marja+W.&rft.au=Rohe%2C+Christan&rft.date=2012-06-08&rft.issn=0009-7330&rft.eissn=1524-4571&rft.volume=110&rft.issue=12&rft.spage=1564&rft.epage=1574&rft_id=info:doi/10.1161%2FCIRCRESAHA.112.269795&rft_id=info%3Apmid%2F22550138&rft.externalDocID=PMC3916111 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0009-7330&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0009-7330&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0009-7330&client=summon |