ArticleEuropean journal of human genetics : EJHG2016
Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function.
Article in European journal of human genetics : EJHG, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Filamin A in focus: unravelling the multifaceted roles of filamin A in neurodevelopment and neurological disorders.Brain : a journal of neurology · 2025Review
- Case Report: genotype-phenotype correlations inFrontiers in genetics · 2025Article
- A unique case of late-onset CIPO caused by a missense mutation in the long isoform ofFrontiers in genetics · 2025Article
- Functional requirement of alternative splicing in epithelial-mesenchymal transition of pancreatic circulating tumor.Molecular therapy. Nucleic acids · 2024Article
- Review
- Article
- Article
- Systematic errors in annotations of truncations, loss-of-function and synonymous variants.Frontiers in genetics · 2023Article
- Smooth muscle motility disorder phenotypes: A systematic review of cases associated with seven pathogenic genes (Intractable & rare diseases research · 2022Review
- Platelet function and filamin A expression in two families with novel FLNA gene mutations associated with periventricular nodular heterotopia and panlobular emphysema.American journal of medical genetics. Part A · 2022Article
- Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome.Orphanet journal of rare diseases · 2021Article
- Visceral myopathy: clinical syndromes, genetics, pathophysiology, and fall of the cytoskeleton.American journal of physiology. Gastrointestinal and liver physiology · 2021Review
- Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.BMC medical genetics · 2020Article
- ExonSkipDB: functional annotation of exon skipping event in human.Nucleic acids research · 2020Article
- Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- FLNA mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature.BMC medical genetics · 2018Article
- Reply to Walsh et al.European journal of human genetics : EJHG · 2017Article
- Update on a previously reported male with a FLNA missense mutation.European journal of human genetics : EJHG · 2017Article
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22 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in filamin A (FLNA) cause an X-linked dominant disorder with multiple organ involvement. Affected females present with periventricular nodular heterotopia (PVNH), cardiovascular complications, thrombocytopenia and Ehlers-Danlos syndrome. These mutations are typically lethal to males, and rare male survivors suffer from failure to thrive, PVNH, and severe cardiovascular and gastrointestinal complications. Here we report two surviving male siblings with a loss-of-function mutation in FLNA. They presented with multiple complications, including valvulopathy, intestinal malrotation and chronic intestinal pseudo-obstruction (CIPO). However, these siblings had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. Trio-based whole-exome sequencing revealed a 4-bp deletion in exon 40 that was predicted to cause a lethal premature protein truncation. However, molecular investigations revealed that the mutation induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses. This study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA.
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