Salazar-Mendiguchía, J;
Barriales-Villa, R;
Lopes, LR;
Ochoa, JP;
Rodríguez-Vilela, A;
Palomino-Doza, J;
Larrañaga-Moreira, JM;
... Monserrat, L; + view all
(2020)
The p.(Cys150Tyr) variant in CSRP3 is associated with late-onset hypertrophic cardiomyopathy in heterozygous individuals.
European Journal of Medical Genetics
, 63
(12)
, Article 104079. 10.1016/j.ejmg.2020.104079.
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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 (p < 0.0001) or in our control population (p < 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 ± 13 years, and the mean left ventricular wall thickness was 18 ± 3 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.
| Type: | Article |
|---|---|
| Title: | The p.(Cys150Tyr) variant in CSRP3 is associated with late-onset hypertrophic cardiomyopathy in heterozygous individuals |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejmg.2020.104079 |
| Publisher version: | http://dx.doi.org/10.1016/j.ejmg.2020.104079 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CSRP3, Cardiomyopathies, Genetics, Hypertrophic cardiomyopathy, z-disk |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10118099 |
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