A New Rare Mutation (691delCC/insAAA) in Exon 17 of the PYGM Gene Causing McArdle Disease

Objective To investigate the genetic effect of a new mutation found in exon 17 of the myophosphorylase ( PYGM ) gene as a cause of McArdle disease (also known as type 5 glycogenosis). Patients A Spanish patient with McArdle disease was screened for 3 common mutations in the PYGM gene (R49X, W797R, and G204S), as previously described. The patient was heterozygous for R49X. To find other mutations, the coding sequence of the entire PYGM gene was sequenced. The carrier status of his relatives was also studied. Results A novel rare mutation was found in codon 691 of exon 17. This is an insertion/deletion (indel) and consists simultaneously of a deletion of 2 bases and an insertion of 3 bases (691delCC/insAAA). A restriction analysis was designed to simplify the detection method. Conclusions The 691delCC/insAAA is the third indel described in the PYGM gene. Indels represent 0.95% of the total reported mutations in the Human Gene Mutation Database. The molecular origin of this mutation is not fully understood. These findings point again to the allelic heterogeneity of McArdle disease.