2. Academic Validation
  3. Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy

Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy

  • Nat Commun. 2014 Oct 29;5:5326. doi: 10.1038/ncomms6326.
Rafael Valdés-Mas 1,  Ana Gutiérrez-Fernández 1,  Juan Gómez 2,  Eliecer Coto 3,  Aurora Astudillo 4,  Diana A Puente 1,  Julián R Reguero 5,  Victoria Álvarez 2,  César Morís 6,  Diego León 5,  María Martín 5,  Xose S Puente 1,  Carlos López-Otín 1
Affiliations

Affiliations

  • 1 Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología-IUOPA, Universidad de Oviedo, 33006 Oviedo, Spain.
  • 2 Genética Molecular, Red de Investigación Renal (REDINREN), 33006 Oviedo, Spain.
  • 3 1] Genética Molecular, Red de Investigación Renal (REDINREN), 33006 Oviedo, Spain [2] Departamento de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain.
  • 4 Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain.
  • 5 Servicio de Cardiología, Fundación Asturcor, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain.
  • 6 1] Departamento de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain [2] Servicio de Cardiología, Fundación Asturcor, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain.
PMID: 25351925 DOI: 10.1038/ncomms6326
Abstract

Mutations in different genes encoding sarcomeric proteins are responsible for 50-60% of familial cases of hypertrophic cardiomyopathy (HCM); however, the genetic alterations causing the disease in one-third of patients are currently unknown. Here we describe a case with familial HCM of unknown cause. Whole-exome Sequencing reveals a variant in the gene encoding the sarcomeric protein filamin C (p.A1539T) that segregates with the disease in this family. Sequencing of 92 HCM cases identifies seven additional variants segregating with the disease in eight families. Patients with FLNC mutations show marked sarcomeric abnormalities in cardiac muscle, and functional analysis reveals that expression of these FLNC variants resulted in the formation of large filamin C aggregates. Clinical studies indicate that FLNC-mutated patients have higher incidence of sudden cardiac death. On the basis of these findings, we conclude that mutations in the gene encoding the sarcomeric protein filamin C cause a new form of familial HMC.

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