Oligonucleotide ligation assay for rapid and sensitive identification of carriers of a missense mutation in the cardiac β-myosin heavy chain gene causing hypertrophic cardiomyopathy in an Indian family

The identification of mutations or sequence polymorphisms in defined segments of genomic DNA is achieved by a variety of molecular methods. The present study illustrates the value of testing for known point mutations in the human cardiac β-myosin heavy chain (MYH7) associated with familial hypertrophic cardiomyopathy (HCM) by the oligonucleotide ligation assay (OLA). We have adapted OLA for the assessment of a G → T transversion in codon 712^Arg-Leu of the β-myosin heavy chain gene, which caused HCM in a previously reported Indian family. This mutation was originally detected by scanning all exons of the MYH7 gene of the index patient by SSCP (single strand conformation polymorphism) and direct DNA sequencing. Carriers of the mutation in the family were determined by OLA (and in parallel by restriction analysis). We conclude that the OLA procedure can be utilized in a nonisotopic format as a simple and rapid procedure to distinguish between 'mutation carriers' and 'nonmutation carriers' in families with known mutations.