Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss‐of‐function filaminopathies

• Published in: Human mutation Vol. 39; no. 1; pp. 103 - 113
• Main Authors: Jenkins, Zandra A, Macharg, Alison, Chang, Cheng‐Yee, Kogelenberg, Margriet, Morgan, Tim, Frentz, Sophia, Wei, Wenhua, Pilch, Jacek, Hannibal, Mark, Foulds, Nicola, McGillivray, George, Leventer, Richard J, García‐Miñaúr, Sixto, Sugito, Stuart, Nightingale, Scott, Markie, David M, Dudding, Tracy, Kapur, Raj P, Robertson, Stephen P
• Format: Journal Article
• Language: English
• Published: United States Hindawi Limited 01.01.2018
• Subjects: 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; filamin A; chronic intestinal pseudo-obstruction; transcriptional regulation; periventricular nodular heterotopia

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...