Clinical Investigations 403Arg-Gln Missence Point Mutation of ß-Myosin-Heavy-Chain in Hypertrophic Cardiomyopathy Families in a Diverse Turkish Population and its Relation with Sudden Cardiac Death

BACKGROUND
Recent identification of mutations in the 1)-myosin-heavy-chain (1)-MHC), a major responsible gene for hypertrophic cardiomyopathy (HCM) has provided the opportunity to characterize genotype-phenotype correlation in HCM families. The goal of this study is the investigation of the 403Arg4Gin missence point mutation in exon 13 of the 14 chromosome of the (3-MHC in patients and relatives of patients in Turkey, from different geographical regions. A further goal is the evaluation of the effects of the genotype on the phenotype as well as the sudden cardiac death (SCD) observed frequently in these cases.
METHODS
The study was carried out on 21 HCM families with 33 cases of HCM (13 females, 21 males) and 108 phenotype-negative relatives (68 females, 40 males), thus on a total of 14ı cases screneed by history, physical examination, electrocardiography and two-dimensional echocardiography. Blood was collected from 32 pts (97%) and 96 relatives (89%) for DNA extraction. Genomic DNA was isolated using DNA extraction kit (Stratagene No: 200600). The gene for B-MHC was amplified from the region of exon ı3 by PCR and followed by Dde I digestion of PCR product and gel electrophoresis and showed the fragments of 84 and 70 bp in normal individuals and four fragments of 84, 70, 52 and 32 in HCM pts.
RESULTS
In 3 (14.2%) of 21 families and 8 (25%) of 32 cases (25%) positive mutation was detected. All phenotype-positive cases in 3 families were found to be positive. The presence of a positive 403Arg4Gin mutation in 2 (2%) phenotype-negative relativesin 2 families with mutation suggests variability in the efficacity of the mutation on the phenotype. SCD was detected in ı2 of 2ı families. It was observed in 2 (66.7%) mutation-positive families and 10 (5.6%) mutation-negative families. Thus SCD occured more frequently in mutation-positive families, although a statistical significance could not be displayed.
CONCLUSIONS
In our study on 403Arg->Gin missence point mutation, carried out for the first time in Turkey, positive mutation was detected in 25% of phenotype-positive cases, and 2% of phenotypenegative relatives; and no significant difference was found between the mutation positive and negative families in terrus of SCD.