Abstract
Inherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical cliniclal presentation of myophosβphorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophorsphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously identified missense mutation Gly204Ser. In another patient, we identified a novel missense mutation Gln665Glu and a singleβbase deletion delA in Lys753. One patient of Turkish ancestry carried a newly identified homozygous AβtoβG transition (ATG to GTG) abolishing the translation initiation codon of the myophosphorylase gene. These results suggest that Arg49Stop also is the most common genetic error associated with myophosphorylase deficiency in the German population. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency among the clinically homogenous patients we studied.