GENETIC EPIDEMIOLOGY OF MUSCULAR-DYSTROPHIES RESULTING FROM SARCOGLYCAN GENE-MUTATIONS

Background-The autosomal recessive limb-girdle muscular dystrophies (L GMDs) are a group of genetically heterogeneous muscle diseases charact erised by progressive proximal Limb muscle weakness. Six different loc i have been mapped and pathogenetic mutations in the genes encoding th e sarcoglycan complex components (alpha-, beta-, gamma-, and delta-sar coglycan) have been documented. LGMD patients affected with primary '' sarcoglycanopathies'' are classified as LGMD2D, 2E, 2C, and 2F, respec tively. Methods-A geographical area in north east Italy (2 319 147 inh abitants) was selected for a genetic epidemiological study on primary sarcoglycanopathies. Within the period 1982 to 1996, all patients livi ng in this region and diagnosed with muscular dystrophy were seen at o ur centre. Immunohistochemical and immunoblot screening for alpha-sarc oglycan protein deficiency was performed on all muscle biopsies from p atients with a progressive muscular dystrophy of unknown aetiology and normal dystrophin. Sarcoglycan mutation analyses were conducted on al l patient muscle biopsies shown to have complete or partial absence of alpha-sarcoglycan immunostaining or a decreased quantity of alpha-sar coglycan protein on immunoblotting. Results-Two hundred and four patie nt muscle biopsies were screened for alpha-sarcoglycan protein deficie ncy and 18 biopsies showed a deficiency. Pathogenetic mutations involv ing one gene for sarcoglycan complex components were identified in 13 patients: alpha-sarcoglycan in seven, beta-sarcoglycan in two, gamma-s arcoglycan in four, and none in the delta-sarcoglycan gene. The overal l prevalence of primary sarcoglycanopathies, as of 31 December 1996, w as estimated to be 5.6 x 10(-6) inhabitants. Conclusion-The prevalence rate estimated in this study is the first to be obtained after bioche mical and molecular genetic screening for sarcoglycan defects.