Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss‐of‐function filaminopathies
Loss‐of‐function mutations in the X‐linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo‐obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is...
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Published in | Human mutation Vol. 39; no. 1; pp. 103 - 113 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.01.2018
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Abstract | Loss‐of‐function mutations in the X‐linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo‐obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is dependent on retention of residual FLNA function but it is unclear why a subgroup of males with mutations in the 5′ end of the gene can present with CIPO alone. Here, we demonstrate evidence for the presence of two FLNA isoforms differing by 28 residues at the N‐terminus initiated at ATG+1 and ATG+82. A male with CIPO (c.18_19del) exclusively expressed FLNA ATG+82, implicating the longer protein isoform (ATG+1) in smooth muscle development. In contrast, mutations leading to reduction of both isoforms are associated with compound phenotypes affecting the brain, heart, and intestine. RNA‐seq data revealed three distinct transcription start sites, two of which produce a protein isoform utilizing ATG+1 while the third utilizes ATG+82. Transcripts sponsoring translational initiation at ATG+1 predominate in intestinal smooth muscle, and are more abundant compared with the level measured in fibroblasts. Together these observations describe a new mechanism of tissue‐specific regulation of FLNA that could reflect the differing mechanical requirements of these cell types during development.
Loss‐of‐function mutations in the X‐linked gene FLNA lead to abnormal neuronal migration, vascular and cardiac defects and congenital intestinal pseudo‐obstruction (CIPO), characterised by anomalous intestinal smooth muscle layering. Males presenting with CIPO alone, are associated with variation in one of two identified transcripts differing by 28 residues at the N‐terminus which is predominately expressed in intestinal smooth muscle. These observations describe a new mechanism of tissue‐specific regulation of FLNA. |
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AbstractList | Loss-of-function mutations in the X-linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo-obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is dependent on retention of residual FLNA function but it is unclear why a subgroup of males with mutations in the 5' end of the gene can present with CIPO alone. Here, we demonstrate evidence for the presence of two FLNA isoforms differing by 28 residues at the N-terminus initiated at ATG
and ATG
. A male with CIPO (c.18_19del) exclusively expressed FLNA ATG
, implicating the longer protein isoform (ATG
) in smooth muscle development. In contrast, mutations leading to reduction of both isoforms are associated with compound phenotypes affecting the brain, heart, and intestine. RNA-seq data revealed three distinct transcription start sites, two of which produce a protein isoform utilizing ATG
while the third utilizes ATG
. Transcripts sponsoring translational initiation at ATG
predominate in intestinal smooth muscle, and are more abundant compared with the level measured in fibroblasts. Together these observations describe a new mechanism of tissue-specific regulation of FLNA that could reflect the differing mechanical requirements of these cell types during development. Loss-of-function mutations in the X-linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo-obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is dependent on retention of residual FLNA function but it is unclear why a subgroup of males with mutations in the 5' end of the gene can present with CIPO alone. Here, we demonstrate evidence for the presence of two FLNA isoforms differing by 28 residues at the N-terminus initiated at ATG+1 and ATG+82 . A male with CIPO (c.18_19del) exclusively expressed FLNA ATG+82 , implicating the longer protein isoform (ATG+1 ) in smooth muscle development. In contrast, mutations leading to reduction of both isoforms are associated with compound phenotypes affecting the brain, heart, and intestine. RNA-seq data revealed three distinct transcription start sites, two of which produce a protein isoform utilizing ATG+1 while the third utilizes ATG+82 . Transcripts sponsoring translational initiation at ATG+1 predominate in intestinal smooth muscle, and are more abundant compared with the level measured in fibroblasts. Together these observations describe a new mechanism of tissue-specific regulation of FLNA that could reflect the differing mechanical requirements of these cell types during development. Loss‐of‐function mutations in the X‐linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo‐obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering. Survival in male hemizygotes for such mutations is dependent on retention of residual FLNA function but it is unclear why a subgroup of males with mutations in the 5′ end of the gene can present with CIPO alone. Here, we demonstrate evidence for the presence of two FLNA isoforms differing by 28 residues at the N‐terminus initiated at ATG+1 and ATG+82. A male with CIPO (c.18_19del) exclusively expressed FLNA ATG+82, implicating the longer protein isoform (ATG+1) in smooth muscle development. In contrast, mutations leading to reduction of both isoforms are associated with compound phenotypes affecting the brain, heart, and intestine. RNA‐seq data revealed three distinct transcription start sites, two of which produce a protein isoform utilizing ATG+1 while the third utilizes ATG+82. Transcripts sponsoring translational initiation at ATG+1 predominate in intestinal smooth muscle, and are more abundant compared with the level measured in fibroblasts. Together these observations describe a new mechanism of tissue‐specific regulation of FLNA that could reflect the differing mechanical requirements of these cell types during development. Loss‐of‐function mutations in the X‐linked gene FLNA lead to abnormal neuronal migration, vascular and cardiac defects and congenital intestinal pseudo‐obstruction (CIPO), characterised by anomalous intestinal smooth muscle layering. Males presenting with CIPO alone, are associated with variation in one of two identified transcripts differing by 28 residues at the N‐terminus which is predominately expressed in intestinal smooth muscle. These observations describe a new mechanism of tissue‐specific regulation of FLNA. |
Author | Morgan, Tim Nightingale, Scott Foulds, Nicola Macharg, Alison Markie, David M Pilch, Jacek Frentz, Sophia Chang, Cheng‐Yee Leventer, Richard J García‐Miñaúr, Sixto Wei, Wenhua Kogelenberg, Margriet Jenkins, Zandra A Sugito, Stuart Dudding, Tracy McGillivray, George Hannibal, Mark Kapur, Raj P Robertson, Stephen P |
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Cites_doi | 10.1038/nsmb.2999 10.1097/PAS.0b013e3181f0ae47 10.1016/S0167-4889(01)00072-6 10.1016/j.gde.2005.04.001 10.1016/j.bpj.2009.04.040 10.1093/brain/awl125 10.1038/ng1119 10.1086/513321 10.1038/ejhg.2015.119 10.1016/j.tibs.2006.05.006 10.1093/nar/gkv054 10.1038/ncb1104-1034 10.1038/nmeth.2019 10.1038/ejhg.2012.209 10.1038/srep32798 10.1074/jbc.M306090200 10.1136/jmg.2005.038505 10.1038/gim.2012.123 10.3748/wjg.14.2953 10.1038/ncomms5656 10.1093/hmg/10.17.1775 10.1038/sj.emboj.7601827 10.1038/ejhg.2008.192 10.1161/ATVBAHA.117.309337 10.1002/ajmg.a.36109 10.1016/j.gtc.2011.09.005 10.1212/01.WNL.0000132818.84827.4D |
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Keywords | filamin A chronic intestinal pseudo-obstruction transcriptional regulation periventricular nodular heterotopia |
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References | 2010; 34 2004; 63 2006; 31 1974; 31 2013; 21 2011; 40 2008; 17 2008; 14 2004; 6 2013; 161A 2012; 15 1996; 58 1992; 51 2003; 33 2016; 6 2014; 5 2004; 279 2009; 97 2017; 37 2006; 43 2015; 22 2015; 43 2007; 80 2001; 1538 2005; 15 2006; 129 2016; 24 2007; 26 2012; 9 2001; 10 Huelsmann (10.1002/humu.23355-BIB0012|humu23355-cit-0012) 2016; 6 Parrini (10.1002/humu.23355-BIB0020|humu23355-cit-0020) 2006; 129 Robertson (10.1002/humu.23355-BIB0024|humu23355-cit-0024) 2003; 33 Sheen (10.1002/humu.23355-BIB0027|humu23355-cit-0027) 2001; 10 Hehr (10.1002/humu.23355-BIB0011|humu23355-cit-0011) 2006; 43 Lad (10.1002/humu.23355-BIB0014|humu23355-cit-0014) 2007; 26 Giorgio (10.1002/humu.23355-BIB0006|humu23355-cit-0006) 2011; 40 Reinstein (10.1002/humu.23355-BIB0022|humu23355-cit-0022) 2013; 21 Schindelin (10.1002/humu.23355-BIB0032|humu23355-cit-0032) 2012; 9 Feng (10.1002/humu.23355-BIB0007|humu23355-cit-0007) 2004; 6 Liu (10.1002/humu.23355-BIB0015|humu23355-cit-0015) 2015; 22 Auricchio (10.1002/humu.23355-BIB0003|humu23355-cit-0003) 1996; 58 Oda (10.1002/humu.23355-BIB0018|humu23355-cit-0018) 2016; 24 Schmoller (10.1002/humu.23355-BIB0026|humu23355-cit-0026) 2009; 97 Gargiulo (10.1002/humu.23355-BIB0008|humu23355-cit-0008) 2007; 80 Tseng (10.1002/humu.23355-BIB0028|humu23355-cit-0028) 2004; 279 Berrou (10.1002/humu.23355-BIB0004|humu23355-cit-0004) 2017; 37 der Werf (10.1002/humu.23355-BIB0030|humu23355-cit-0030) 2012; 15 Allen (10.1002/humu.23355-BIB0001|humu23355-cit-0001) 1992; 51 Oegema (10.1002/humu.23355-BIB0019|humu23355-cit-0019) 2013; 161A Popowicz (10.1002/humu.23355-BIB0021|humu23355-cit-0021) 2006; 31 Clayton-Smith (10.1002/humu.23355-BIB0005|humu23355-cit-0005) 2008; 17 Kapur (10.1002/humu.23355-BIB0013|humu23355-cit-0013) 2010; 34 Guerrini (10.1002/humu.23355-BIB0009|humu23355-cit-0009) 2004; 63 Royer (10.1002/humu.23355-BIB0025|humu23355-cit-0025) 1974; 31 der Flier (10.1002/humu.23355-BIB0029|humu23355-cit-0029) 2001; 1538 Nakamura (10.1002/humu.23355-BIB0017|humu23355-cit-0017) 2014; 5 Antonucci (10.1002/humu.23355-BIB0002|humu23355-cit-0002) 2008; 14 Haberle (10.1002/humu.23355-BIB0010|humu23355-cit-0010) 2015; 43 Robertson (10.1002/humu.23355-BIB0023|humu23355-cit-0023) 2005; 15 |
References_xml | – volume: 14 start-page: 2953 issue: 19 year: 2008 end-page: 2961 article-title: Chronic intestinal pseudo‐obstruction publication-title: World Journal of Gastroenterology – volume: 10 start-page: 1775 issue: 17 year: 2001 end-page: 1783 article-title: Mutations in the X‐linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females publication-title: Human Molecular Genetics – volume: 97 start-page: 83 issue: 1 year: 2009 end-page: 89 article-title: Structural and viscoelastic properties of actin/filamin networks: Cross‐linked versus bundled networks publication-title: Biophysical Journal – volume: 129 start-page: 1892 issue: Pt 7 year: 2006 end-page: 1906 article-title: Periventricular heterotopia: Phenotypic heterogeneity and correlation with Filamin A mutations publication-title: Brain: A Journal of Neurology – volume: 5 start-page: 4656 year: 2014 article-title: Documentation and localization of force‐mediated filamin A domain perturbations in moving cells publication-title: Nature Communications – volume: 80 start-page: 751 issue: 4 year: 2007 end-page: 758 article-title: Filamin A is mutated in X‐linked chronic idiopathic intestinal pseudo‐obstruction with central nervous system involvement publication-title: American Journal of Human Genetics – volume: 15 start-page: 301 issue: 3 year: 2005 end-page: 307 article-title: Filamin A: Phenotypic diversity publication-title: Current Opinion in Genetics & Development – volume: 40 start-page: 787 issue: 4 year: 2011 end-page: 807 article-title: Chronic intestinal pseudo‐obstruction: Clinical features, diagnosis, and therapy publication-title: Gastroenterology Clinics of North America – volume: 161A start-page: 2376 issue: 9 year: 2013 end-page: 2384 article-title: Novel no‐stop FLNA mutation causes multi‐organ involvement in males publication-title: American Journal of Medical Genetics. Part A – volume: 43 issue: 8 year: 2015 article-title: CAGEr: Precise TSS data retrieval and high‐resolution promoterome mining for integrative analyses publication-title: Nucleic Acids Research – volume: 31 start-page: 223 issue: 2 year: 1974 end-page: 229 article-title: [The familial syndrome of short small intestine with intestinal malrotation and hypertrophic stenosis of the pylorus in infants] publication-title: Archives Francaises De Pediatrie – volume: 58 start-page: 743 issue: 4 year: 1996 end-page: 748 article-title: The locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28 publication-title: American Journal of Human Genetics – volume: 26 start-page: 3993 issue: 17 year: 2007 end-page: 4004 article-title: Structure of three tandem filamin domains reveals auto‐inhibition of ligand binding publication-title: The EMBO Journal – volume: 34 start-page: 1528 issue: 10 year: 2010 end-page: 1543 article-title: Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x‐linked intestinal pseudo‐obstruction publication-title: The American Journal of Surgical Pathology – volume: 9 start-page: 676 issue: 7 year: 2012 end-page: 682 article-title: Fiji: an open‐source platform for biological‐image analysis publication-title: Nature Methods – volume: 15 start-page: 310 issue: 4 year: 2012 end-page: 313 article-title: Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations publication-title: Genetics in Medicine – volume: 33 start-page: 487 issue: 4 year: 2003 end-page: 491 article-title: Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans publication-title: Nature Genetics – volume: 31 start-page: 411 issue: 7 year: 2006 end-page: 419 article-title: Filamins: Promiscuous organizers of the cytoskeleton publication-title: Trends in Biochemical Sciences – volume: 6 start-page: 32798 year: 2016 article-title: Evidence for the mechanosensor function of filamin in tissue development publication-title: Scientific Reports – volume: 43 start-page: 541 issue: 6 year: 2006 end-page: 544 article-title: A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro‐fronto‐facial syndrome publication-title: Journal of Medical Genetics – volume: 21 start-page: 494 issue: 5 year: 2013 end-page: 502 article-title: Vascular and connective tissue anomalies associated with X‐linked periventricular heterotopia due to mutations in Filamin A publication-title: European Journal of Human Genetics – volume: 17 start-page: 434 issue: 4 year: 2008 end-page: 443 article-title: Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance publication-title: European Journal of Human Genetics – volume: 22 start-page: 383 issue: 5 year: 2015 end-page: 389 article-title: Structural mechanism of integrin inactivation by filamin publication-title: Nature Structural & Molecular Biology – volume: 37 start-page: 1087 issue: 6 year: 2017 end-page: 1097 article-title: Gain‐of‐function mutation in filamin A potentiates platelet integrin alphaIIbbeta3 activation publication-title: Arteriosclerosis, Thrombosis, and Vascular Biology – volume: 51 start-page: 1229 issue: 6 year: 1992 end-page: 1239 article-title: Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen‐receptor gene correlates with X chromosome inactivation publication-title: American Journal of Human Genetics – volume: 6 start-page: 1034 issue: 11 year: 2004 end-page: 1038 article-title: The many faces of filamin: A versatile molecular scaffold for cell motility and signalling publication-title: Nature Cell Biology – volume: 24 start-page: 408 issue: 3 year: 2016 end-page: 414 article-title: Exon skipping causes atypical phenotypes associated with a loss‐of‐function mutation in FLNA by restoring its protein function publication-title: European Journal of Human Genetics – volume: 1538 start-page: 99 issue: 2–3 year: 2001 end-page: 117 article-title: Structural and functional aspects of filamins publication-title: Biochimica et Biophysica Acta – volume: 63 start-page: 51 issue: 1 year: 2004 end-page: 56 article-title: Germline and mosaic mutations of FLN1 in men with periventricular heterotopia publication-title: Neurology – volume: 279 start-page: 1819 issue: 3 year: 2004 end-page: 1826 article-title: The bimodal role of filamin in controlling the architecture and mechanics of F‐actin networks publication-title: The Journal of Biological Chemistry – volume: 22 start-page: 383 issue: 5 year: 2015 ident: 10.1002/humu.23355-BIB0015|humu23355-cit-0015 article-title: Structural mechanism of integrin inactivation by filamin publication-title: Nature Structural & Molecular Biology doi: 10.1038/nsmb.2999 contributor: fullname: Liu – volume: 34 start-page: 1528 issue: 10 year: 2010 ident: 10.1002/humu.23355-BIB0013|humu23355-cit-0013 article-title: Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-linked intestinal pseudo-obstruction publication-title: The American Journal of Surgical Pathology doi: 10.1097/PAS.0b013e3181f0ae47 contributor: fullname: Kapur – volume: 1538 start-page: 99 issue: 2-3 year: 2001 ident: 10.1002/humu.23355-BIB0029|humu23355-cit-0029 article-title: Structural and functional aspects of filamins publication-title: Biochimica et Biophysica Acta doi: 10.1016/S0167-4889(01)00072-6 contributor: fullname: der Flier – volume: 15 start-page: 301 issue: 3 year: 2005 ident: 10.1002/humu.23355-BIB0023|humu23355-cit-0023 article-title: Filamin A: Phenotypic diversity publication-title: Current Opinion in Genetics & Development doi: 10.1016/j.gde.2005.04.001 contributor: fullname: Robertson – volume: 97 start-page: 83 issue: 1 year: 2009 ident: 10.1002/humu.23355-BIB0026|humu23355-cit-0026 article-title: Structural and viscoelastic properties of actin/filamin networks: Cross-linked versus bundled networks publication-title: Biophysical Journal doi: 10.1016/j.bpj.2009.04.040 contributor: fullname: Schmoller – volume: 129 start-page: 1892 issue: Pt 7 year: 2006 ident: 10.1002/humu.23355-BIB0020|humu23355-cit-0020 article-title: Periventricular heterotopia: Phenotypic heterogeneity and correlation with Filamin A mutations publication-title: Brain: A Journal of Neurology doi: 10.1093/brain/awl125 contributor: fullname: Parrini – volume: 33 start-page: 487 issue: 4 year: 2003 ident: 10.1002/humu.23355-BIB0024|humu23355-cit-0024 article-title: Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans publication-title: Nature Genetics doi: 10.1038/ng1119 contributor: fullname: Robertson – volume: 80 start-page: 751 issue: 4 year: 2007 ident: 10.1002/humu.23355-BIB0008|humu23355-cit-0008 article-title: Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement publication-title: American Journal of Human Genetics doi: 10.1086/513321 contributor: fullname: Gargiulo – volume: 24 start-page: 408 issue: 3 year: 2016 ident: 10.1002/humu.23355-BIB0018|humu23355-cit-0018 article-title: Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function publication-title: European Journal of Human Genetics doi: 10.1038/ejhg.2015.119 contributor: fullname: Oda – volume: 31 start-page: 411 issue: 7 year: 2006 ident: 10.1002/humu.23355-BIB0021|humu23355-cit-0021 article-title: Filamins: Promiscuous organizers of the cytoskeleton publication-title: Trends in Biochemical Sciences doi: 10.1016/j.tibs.2006.05.006 contributor: fullname: Popowicz – volume: 58 start-page: 743 issue: 4 year: 1996 ident: 10.1002/humu.23355-BIB0003|humu23355-cit-0003 article-title: The locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28 publication-title: American Journal of Human Genetics contributor: fullname: Auricchio – volume: 43 issue: 8 year: 2015 ident: 10.1002/humu.23355-BIB0010|humu23355-cit-0010 article-title: CAGEr: Precise TSS data retrieval and high-resolution promoterome mining for integrative analyses publication-title: Nucleic Acids Research doi: 10.1093/nar/gkv054 contributor: fullname: Haberle – volume: 6 start-page: 1034 issue: 11 year: 2004 ident: 10.1002/humu.23355-BIB0007|humu23355-cit-0007 article-title: The many faces of filamin: A versatile molecular scaffold for cell motility and signalling publication-title: Nature Cell Biology doi: 10.1038/ncb1104-1034 contributor: fullname: Feng – volume: 9 start-page: 676 issue: 7 year: 2012 ident: 10.1002/humu.23355-BIB0032|humu23355-cit-0032 article-title: Fiji: an open-source platform for biological-image analysis publication-title: Nature Methods doi: 10.1038/nmeth.2019 contributor: fullname: Schindelin – volume: 21 start-page: 494 issue: 5 year: 2013 ident: 10.1002/humu.23355-BIB0022|humu23355-cit-0022 article-title: Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A publication-title: European Journal of Human Genetics doi: 10.1038/ejhg.2012.209 contributor: fullname: Reinstein – volume: 6 start-page: 32798 year: 2016 ident: 10.1002/humu.23355-BIB0012|humu23355-cit-0012 article-title: Evidence for the mechanosensor function of filamin in tissue development publication-title: Scientific Reports doi: 10.1038/srep32798 contributor: fullname: Huelsmann – volume: 279 start-page: 1819 issue: 3 year: 2004 ident: 10.1002/humu.23355-BIB0028|humu23355-cit-0028 article-title: The bimodal role of filamin in controlling the architecture and mechanics of F-actin networks publication-title: The Journal of Biological Chemistry doi: 10.1074/jbc.M306090200 contributor: fullname: Tseng – volume: 43 start-page: 541 issue: 6 year: 2006 ident: 10.1002/humu.23355-BIB0011|humu23355-cit-0011 article-title: A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro-fronto-facial syndrome publication-title: Journal of Medical Genetics doi: 10.1136/jmg.2005.038505 contributor: fullname: Hehr – volume: 15 start-page: 310 issue: 4 year: 2012 ident: 10.1002/humu.23355-BIB0030|humu23355-cit-0030 article-title: Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations publication-title: Genetics in Medicine doi: 10.1038/gim.2012.123 contributor: fullname: der Werf – volume: 14 start-page: 2953 issue: 19 year: 2008 ident: 10.1002/humu.23355-BIB0002|humu23355-cit-0002 article-title: Chronic intestinal pseudo-obstruction publication-title: World Journal of Gastroenterology doi: 10.3748/wjg.14.2953 contributor: fullname: Antonucci – volume: 31 start-page: 223 issue: 2 year: 1974 ident: 10.1002/humu.23355-BIB0025|humu23355-cit-0025 article-title: [The familial syndrome of short small intestine with intestinal malrotation and hypertrophic stenosis of the pylorus in infants] publication-title: Archives Francaises De Pediatrie contributor: fullname: Royer – volume: 5 start-page: 4656 year: 2014 ident: 10.1002/humu.23355-BIB0017|humu23355-cit-0017 article-title: Documentation and localization of force-mediated filamin A domain perturbations in moving cells publication-title: Nature Communications doi: 10.1038/ncomms5656 contributor: fullname: Nakamura – volume: 10 start-page: 1775 issue: 17 year: 2001 ident: 10.1002/humu.23355-BIB0027|humu23355-cit-0027 article-title: Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females publication-title: Human Molecular Genetics doi: 10.1093/hmg/10.17.1775 contributor: fullname: Sheen – volume: 26 start-page: 3993 issue: 17 year: 2007 ident: 10.1002/humu.23355-BIB0014|humu23355-cit-0014 article-title: Structure of three tandem filamin domains reveals auto-inhibition of ligand binding publication-title: The EMBO Journal doi: 10.1038/sj.emboj.7601827 contributor: fullname: Lad – volume: 17 start-page: 434 issue: 4 year: 2008 ident: 10.1002/humu.23355-BIB0005|humu23355-cit-0005 article-title: Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance publication-title: European Journal of Human Genetics doi: 10.1038/ejhg.2008.192 contributor: fullname: Clayton-Smith – volume: 37 start-page: 1087 issue: 6 year: 2017 ident: 10.1002/humu.23355-BIB0004|humu23355-cit-0004 article-title: Gain-of-function mutation in filamin A potentiates platelet integrin alphaIIbbeta3 activation publication-title: Arteriosclerosis, Thrombosis, and Vascular Biology doi: 10.1161/ATVBAHA.117.309337 contributor: fullname: Berrou – volume: 161A start-page: 2376 issue: 9 year: 2013 ident: 10.1002/humu.23355-BIB0019|humu23355-cit-0019 article-title: Novel no-stop FLNA mutation causes multi-organ involvement in males publication-title: American Journal of Medical Genetics. Part A doi: 10.1002/ajmg.a.36109 contributor: fullname: Oegema – volume: 40 start-page: 787 issue: 4 year: 2011 ident: 10.1002/humu.23355-BIB0006|humu23355-cit-0006 article-title: Chronic intestinal pseudo-obstruction: Clinical features, diagnosis, and therapy publication-title: Gastroenterology Clinics of North America doi: 10.1016/j.gtc.2011.09.005 contributor: fullname: Giorgio – volume: 51 start-page: 1229 issue: 6 year: 1992 ident: 10.1002/humu.23355-BIB0001|humu23355-cit-0001 article-title: Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation publication-title: American Journal of Human Genetics contributor: fullname: Allen – volume: 63 start-page: 51 issue: 1 year: 2004 ident: 10.1002/humu.23355-BIB0009|humu23355-cit-0009 article-title: Germline and mosaic mutations of FLN1 in men with periventricular heterotopia publication-title: Neurology doi: 10.1212/01.WNL.0000132818.84827.4D contributor: fullname: Guerrini |
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SubjectTerms | Adolescent Brain - abnormalities Brain - diagnostic imaging Cell migration Child chronic intestinal pseudo‐obstruction Conserved Sequence DNA Mutational Analysis Female Fibroblasts filamin A Filamins - chemistry Filamins - genetics Filamins - metabolism Gastrointestinal Tract - metabolism Gene Expression Genetic Association Studies Genetic Heterogeneity Heart diseases Humans Intestine Isoforms Loss of Function Mutation Magnetic Resonance Imaging Male Muscle, Smooth - metabolism Mutation N-Terminus periventricular nodular heterotopia Phenotype Protein Isoforms Ribonucleic acid RNA Smooth muscle Transcription Transcription, Genetic transcriptional regulation Translation initiation Young Adult |
Title | Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss‐of‐function filaminopathies |
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