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 r...

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Detalles Bibliográficos
Autores: Salazar Mendiguchía, Joel, Ochoa, Juan Pablo, Palomino Doza, Julián, Domínguez, Fernando, Díez López, Carles, Akhtar, Mohammed, Ramiro León, Soraya, Clemente, María M., Pérez Cejas, Antonia, Robledo, María, Gómez Díaz, Iria, Peña Peña, María Luisa, Climent, Vicente, Salmerón Martínez, Francisco, Hernández, Celestino, García Granja, Pablo Elpidio, Mogollón, M. Victoria, Cárdenas Reyes, Ivonne, Cicerchia, Marcos, García Giustiniani, Diego, Lamounier Jr., Arsonval, Gil Fournier, Belén, Díaz Flores, Felícitas, Salguero, Rafael, Santomé, Luis, Syrris, Petros, Olivé i Plana, Montserrat, Garcia Pavia, Pablo, Ortiz Genga, Martín, Elliott, Perry M., Monserrat, Lorenzo, Genescopic Research Group
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/174053
Acceso en línea:https://hdl.handle.net/2445/174053
Access Level:acceso abierto
Palabra clave:Miocardiopaties
Mutació (Biologia)
Myocardiopathies
Mutation (Biology)
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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