MOLECULAR CHARACTERIZATION OF MYOPHOSPHORYLASE DEFICIENCY IN A GROUP OF PATIENTS FROM NORTHERN ITALY

We studied a group of 14 patients from Northern Italy with myophosphor ylase deficiency. The disease presented considerable clinical and bioc hemical heterogenity, which was reflected at the molecular level. The clinical presentation was typical in 3 patients, mild in 7 (exercise i ntolerance), and severe in 4 (fixed weakness). Enzyme activity was und etectable in 10 patients, below 3% of control in 3, and 13% of control in one. Enzymatic protein was detectable immunologically only in 1 pa tient. Myophosphorylase mRNA was present in 8 patients, but in 7 of th em it was reduced in amount. Two patients were homozygous for the comm on nonsense R49X mutation, 5 were heterozygous. Two missense mutations not previously observed were identified in this group of patients. Th e frequency of alleles with the R49X mutation was significantly lower in this group of patients than in previously reported series. Myophosp horylase deficiency is genetically heterogeneous even among patients l iving in a small region and with a common ethnic background.