Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations

LMNA mutations have been associated with familial or sporadic dilated cardiomyopathy (DC), with or without conduction system disease. We studied the LMNA gene in 67 consecutive patients with DC (18 had familial DC, 17 had possible familial DC, and 32 sporadic DC). From genomic DNA, coding regions of the LMNA gene were amplified by polymerase chain reaction, studied by single-strand conformation polymorphism, and cycle sequenced. Mutations were confirmed by restriction fragment length polymorphism. Two disease-causing mutations were found in families A and B. In family A, a novel R349L mutation was present in the mother and her identical twin daughters. They required cardiac transplantation at 36, 18, and 20 years of age. In family B, the R190W mutation was present in 2 cousins with DC and without conduction system disease (1 had cardiac transplantation at 45 years of age and 1 died suddenly at 46 years of age) and in 2 of their sons. The mothers of the 2 affected patients died due to cardiac causes in their 40s (1 died suddenly). One of the carriers fulfilled diagnostic criteria for isolated left ventricular noncompaction. Our data associated the R349L and R190W mutations in LMNA with severe forms of familial DC. LMNA mutations should be considered in the genetic screening of patients with familial DC without conduction system disease. Isolated left ventricular noncompaction may be part of the phenotypic spectrum of the laminopathies.