The p.(Cys150Tyr) variant in CSRP3 is associated with late-onset hypertrophic cardiomyopathy in heterozygous individuals.
Eur J Med Genet
; 63(12): 104079, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33035702
ABSTRACT
INTRODUCTION AND OBJECTIVES:
Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. Mutations in CSRP3 have been associated with HCM, but evidence supporting pathogenicity is inconclusive. In this study, we describe an HCM cohort with a missense variant in CSRP3 (p.Cys150Tyr) with supporting evidence for pathogenicity and a description of the associated phenotype.METHODS:
CSRP3 was sequenced in 6456 index cases with a diagnosis of HCM and in 5012 probands with other cardiomyopathies. In addition, 3372 index cases with hereditary cardiovascular disorders other than cardiomyopathies (mainly channelopathies and aortopathies) were used as controls.RESULTS:
The p.(Cys150Tyr) variant was identified in 11 unrelated individuals of the 6456 HCM probands, and it was not identified in patients with other cardiomyopathies (pâ¯<â¯0.0001) or in our control population (pâ¯<â¯0.0001). Ten of the index cases were heterozygous and one was homozygous. Homozygous had a more severe phenotype. Family screening identified 17 other carriers. Wild-type individuals showed no signs of disease. The mean age at diagnosis of affected individuals was 55⯱â¯13 years, and the mean left ventricular wall thickness was 18⯱â¯3â¯mm. The variant showed highly age-dependent penetrance. After a mean follow-up of 11 (±8) years, no adverse events were reported in any of the HCM patients.CONCLUSIONS:
The p.(Cys150Tyr) variant in CSRP3 causes late-onset and low risk form of hypertrophic cardiomyopathy in heterozygous carriers.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
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Penetrância
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Proteínas com Domínio LIM
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Proteínas Musculares
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Med Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article