Unusual laminin alpha 2 processing in myoblasts from a patient with a novel variant of congenital muscular dystrophy

We recently described a novel congenital muscular dystrophy (CMD) syndrome characterized by mental retardation, microcephaly, and partial merosin defi ciency on muscle biopsy. Linkage analysis excluded involvement of the known CMD loci. We now report on a study performed on the differentiation of cul tured myoblasts from one patient affected by this condition to evaluate the potential to form myotubes and merosin processing in these cells. The diff erentiation rate was comparable to controls and myotubes were stable in cul ture. Biochemical analysis showed the expected 80-kDa merosin subunit in my oblasts. However, a shifted 60-kDa protein was detected in myotubes, Matrix -metalloproteinases (MMPs) zymography showed increased gelatinolytic activi ty, and immunoblotting identified an increased amount of membrane-type 1 ma trix-metalloproteinase in pathological myotube preparations. Our results sh ow that these CMD-derived myotubes contain a low molecular weight merosin. They further suggest that an altered regulation of MMPs can be involved in basal lamina damage, (C) 2000 Academic Press.