文摘
Summary
The group of autosomal recessive (AR) muscular dystrophies includes, among others, two main clinical entities, the limb-girdle muscular dystrophies (LGMDs) and the distal muscular dystrophies. The former are characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. This clinical heterogeneity has been demonstrated at the molecular level, since the genes for six AR forms have been cloned and/or have been mapped to 15q15.1 (LGMD2A), 2p12-16 (LGMD2B), 13q12 (LGMD2C), 17q12-q21.33 (LGMD2D), 4q12 (LGMD2E), and 5q33-34 (LGMD2F). The AR distal muscular dystrophies originally included two subgroups, Miyoshi myopathy, characterized mainly by extremely elevated serum creatine kinase (CK) activity and by a dystrophic muscle pattern, and Nonaka myopathy, which is distinct from the others because of the normal to slightly elevated serum CK levels and a myopathic muscle pattern with rimmed vac-uoles. With regard to our unclassified AR LGMD families, analysis of the affected sibs from one of them (family LG61) revealed some clinical and laboratory findings (early involvement of the distal muscles, mildly elevated serum CK levels, and rimmed vacuoles in muscle biopsies) that usually are not observed in the analysis of patients with LGMD2A—LGMD2F. In the present investigation, through a genomewide search in family LG61, we demonstrated linkage of the allele causing this form of muscular dystrophy to a 3-cM region on 17q11-12. We suggest that this form, which, interestingly, clinically resembles AR Kugelberg-Welander disease, should be classified as LGMD2G. In addition, our results indicate the existence of still another locus causing severe LGMD.
