PT  - JOURNAL ARTICLE
AU  - Joel Salazar-Mendiguchía
AU  - Juan Pablo Ochoa
AU  - Julian Palomino-Doza
AU  - Fernando Domínguez
AU  - Carles Díez-López
AU  - Mohammed Akhtar
AU  - Soraya Ramiro-León
AU  - María M Clemente
AU  - Antonia Pérez-Cejas
AU  - María Robledo
AU  - Iria Gómez-Díaz
AU  - María Luisa Peña-Peña
AU  - Vicente Climent
AU  - Francisco Salmerón-Martínez
AU  - Celestino Hernández
AU  - Pablo E García-Granja
AU  - M Victoria Mogollón
AU  - Ivonne Cárdenas-Reyes
AU  - Marcos Cicerchia
AU  - Diego García-Giustiniani
AU  - Arsonval Lamounier Jr.
AU  - Belén Gil-Fournier
AU  - Felícitas Díaz-Flores
AU  - Rafael Salguero
AU  - Luis Santomé
AU  - Petros Syrris
AU  - Montse Olivé
AU  - Pablo García-Pavía
AU  - Martín Ortiz-Genga
AU  - Perry M. Elliott
AU  - Lorenzo Monserrat
AU  - on behalf of GENESCOPIC Research Group
TI  - Mutations in <em>TRIM63</em> cause an autosomal-recessive form of hypertrophic cardiomyopathy
AID  - 10.1136/heartjnl-2020-316913
DP  - 2020 Sep 01
TA  - Heart
PG  - 1342--1348
VI  - 106
IP  - 17
4099  - http://heart.bmj.com/content/106/17/1342.short
4100  - http://heart.bmj.com/content/106/17/1342.full
SO  - Heart2020 Sep 01; 106
AB  - 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.