Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy

Objective Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the re...

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Detalles Bibliográficos
Autores: Salazar-Mendiguchiá, Joel, Ochoa, Juan Pablo, Palomino-Doza, Julian, Domínguez, Fernando, Diéz-López, Carles, Akhtar, Mohammed, Ramiro-León, Soraya, Clemente, Mariá M., Pérez-Cejas, Antonia, Robledo, Mariá, Gómez-Diáz, Iria, Peña-Peña, Mariá Luisa, Climent, Vicente, Salmerón-Martínez, Francisco, Hernández, Celestino, Garciá-Granja, Pablo E., Mogollón, M. Victoria, Cárdenas-Reyes, Ivonne, Cicerchia, Marcos, Garciá-Giustiniani, Diego, Lamounier, Arsonval, Gil-Fournier, Belén, Diáz-Flores, Felícitas, Salguero, Rafael, Santomé, Luis, Syrris, Petros, Olivé, Montse, García Pavía, Pablo, Ortiz-Genga, Martín, Elliott, Perry M., Monserrat, Lorenzo, Behalf of GENESCOPIC Research Group
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/694170
Acceso en línea:http://hdl.handle.net/10486/694170
https://dx.doi.org/10.1136/heartjnl-2020-316913
Access Level:acceso abierto
Palabra clave:familial cardiomyopathies
genetics
hypertrophic cardiomyopathy
Medicina
Descripción
Sumario:Objective Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. Methods TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. Results Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). Conclusion TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

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