Format

Send to

Choose Destination
Nat Commun. 2014 Oct 29;5:5326. doi: 10.1038/ncomms6326.

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

Author information

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.

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.

PMID:
25351925
DOI:
10.1038/ncomms6326
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center