ClinVar

In 2 French kindreds with chromosome 11-linked hypertrophic cardiomyopathy (115197), Bonne et al. (1995) found 2 cDNAs of different lengths, 336 bp and 196 bp, in affected individuals. Direct sequencing of the 336 nucleotide product gave 2 different sequences; the normal cDNA and a cDNA with an 11-bp deletion between nucleotides 1960 and 1970. Sequencing of the 196-bp product gave a cDNA with a 140-bp deletion between positions 1960 and 2099. Both deletions resulted in a frameshift followed by a premature stop codon. Studies of genomic DNA revealed an A-to-G transition at a 3-prime splice acceptor site in affected individuals. This mutation accounted for both aberrant transcripts since the 140-bp deletion resulted from skipping the exon that spans positions 1060 to 2099, while the 11-bp deletion resulted from the use of a cryptic splice site downstream from the normal splice site that had been inactivated. The A-to-G transition mutation introduced a new NlaIV restriction site which was used to screen affected and unaffected individuals.