A novel splice-site mutation in the STA gene in a Japanese patient with Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive or autosomal dominant progressive muscular dystrophy characterized by progressive muscle wasting and weakness with scapulo-humero-peroneal distribution, early contracture and cardiomyopathy with conduction block. The responsible gene for EDMD, designated as 'STA', has been mapped to Xq 28 and cloned. It encodes a serine-rich protein of 254-amino-acid, called 'emerin', localized in the inner nuclear rim. We performed genetic analysis of a 23- year-old male clinically diagnosed as EDMD and found a novel point mutation. Total RNA was extracted from skeletal muscle and reverse-transcription and polymerase chain reaction amplification was performed using a set of oligonucleotide primers between 5' -flanking site of exon 1 and exon 4. Our patient gave a smaller PCR product (about 30 bp) than normal control. The determined cDNA sequence revealed a deletion of 29 bp, spanning position 164 to 192 in exon 1. To clarify the mutant allele, we performed genomic DNA sequence. Genomic DNA sequence from the initiation of exon 1 to the upstream lesion of exon 2 confirmed a novel point mutation G to C, at nucleotide 197 in the donor splice site of intron 1. This point mutation may interfere with the correct splicing of the mRNA and cause frameshift, resulted in truncation of predicted protein by premature stop. We report a novel point mutation G to C, at nucleotide 197 in the intron 1 of STA gene corresponding the truncation of predicted protein, which differs from any of the previously reported mutations.