Isolated X-linked hypertrophic cardiomyopathy caused by a novel mutation of the four-and-a-half LIM domain 1 gene
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24114807
DOI
10.1161/circgenetics.113.000245
PII: CIRCGENETICS.113.000245
Knihovny.cz E-zdroje
- Klíčová slova
- cardiomyopathy, hypertrophic, exome, heart failure, diastolic,
- MeSH
- dospělí MeSH
- elektrokardiografie MeSH
- elektronová mikroskopie MeSH
- genetická predispozice k nemoci genetika MeSH
- geny vázané na chromozom X genetika MeSH
- hypertrofická kardiomyopatie genetika metabolismus patofyziologie MeSH
- imunohistochemie MeSH
- intracelulární signální peptidy a proteiny genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mutace * MeSH
- myokard metabolismus patologie ultrastruktura MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteiny s doménou LIM genetika metabolismus MeSH
- rodokmen MeSH
- senioři nad 80 let MeSH
- svalové proteiny genetika metabolismus MeSH
- zdraví rodiny MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- FHL1 protein, human MeSH Prohlížeč
- intracelulární signální peptidy a proteiny MeSH
- proteiny s doménou LIM MeSH
- svalové proteiny MeSH
BACKGROUND: Hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction has been associated with marked exercise intolerance and poor prognosis. However, molecular pathogenesis of this phenotype remains unexplained in a large proportion of cases. METHODS AND RESULTS: We performed whole exome sequencing as an initial genetic test in a large Czech family with 3 males affected by nonobstructive hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction in end-stage disease. A novel frameshift mutation of four-and-a-half LIM domain 1 gene (FHL1) (c.599_600insT; p.F200fs32X) was detected in these individuals. The mutation does not affect transcription, splicing, and stability of FHL1 mRNA and results in production of truncated FHL1 protein, which is contrary to heart tissue homogenate not detectable in frozen tissue sections of myocardial biopsy of affected males. The identified mutation cosegregated also with abnormal ECG and with 1 case of apical hypertrophic cardiomyopathy in heterozygous females. Although skeletal muscle involvement is a common finding in FHL1-related diseases, we could exclude myopathy in all mutation carriers. CONCLUSIONS: We identified a novel FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.
Citace poskytuje Crossref.org
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