Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy
Salazar-Mendiguchía, Joel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Ochoa, Juan Pablo (Health in Code)
Palomino-Doza, Julian (Instituto de Salud Carlos III)
Domınguez, Fernando (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Díez-López, Carles (Hospital Universitari de Bellvitge)
Akhtar, Mohammed (St Bartholomew's Hospital (Regne Unit))
Ramiro-León, Soraya (Hospital Universitario de Getafe (Madrid))
Clemente, María M. (Hospital Virgen del Puerto)
Pérez-Cejas, Antonia (Hospital Universitario de Canarias (La Laguna))
Robledo, María (Hospital Txagorritxu)
Gómez-Díaz, Iria (Health in Code)
Peña-Peña, María Luisa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Climent, Vicente (Hospital General Universitario de Alicante (Alacant, País Valencià))
Salmerón-Martínez, Francisco (Complejo Hospitalario Universitario de Albacete)
Hernández, Celestino (Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife))
García-Granja, Pablo Elpidio (Hospital Clínico Universitario de Valladolid)
Mogollón, M. Victoria (Hospital San Pedro de Alcántara)
Cárdenas-Reyes, Ivonne (Health in Code)
Cicerchia, Marcos (Health in Code)
García-Giustiniani, Diego (Health in Code)
Lamounier Jr., Arsonval (Health in Code)
Gil-Fournier, Belén (Hospital Universitario de Getafe (Madrid))
Díaz-Flores, Felícitas (Hospital Universitario de Canarias (La Laguna))
Salguero, Rafael (Hospital Universitario 12 de Octubre (Madrid))
Santomé, Luis (Health in Code)
Syrris, Petros (University College London)
Olivé, Montse (Hospital Universitari de Bellvitge)
García-Pavía, Pablo (University Francisco de Vitoria (UFV))
Ortiz-Genga, Martín (Health in Code)
Elliott, Perry M. (University College London)
Monserrat, Lorenzo (Health in Code)

Fecha:	2020
Resumen:	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. 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. 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%). 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Hypertrophic cardiomyopathy ; Familial cardiomyopathies ; Genetics
Publicado en:	Heart, Vol. 106, Issue 17 (September 2020) , p. 1342-1348, ISSN 1468-201X

DOI: 10.1136/heartjnl-2020-316913
PMID: 32451364

7 p, 557.1 KB

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