Sarcoglycanopathies are responsible for 68% of severe autosomal recessive limb-girdle muscular dystrophy in the Brazilian population

Sarcoglycanopathies (SGPs) constitute a subgroup of limb-girdle muscular dy strophies (LGMD). where the primary defect in one sarcoglycan (SG) glycopro tein (alpha-SG, beta-SG, gamma-SG or delta-SG) results in a deficiency of t he whole complex. Four genes, at 17q, 4q, 13q and 5q, encode the four glyco proteins, and mutations in these genes cause diseases called LGMD2D. 2E, 2C and 2F. To estimate the prevalence, relative proportions and clinical feat ures of SGPs, we have studied the SG proteins in muscle biopsies of 140 pat ients (from 115 unrelated Brazilian families) with a clinical diagnosis of LGMD. alpha-SG immunofluorescence analysis showed a positive staining patte rn in 70% (80/115) of the families, a patchy pattern in 14% (16/115) and a negative pattern in 16% (19/115) of the families. All the 19 alpha-SG negat ive, and four of the 16 alpha-SG patchy patients were also deficient for th e other three SG proteins, confirming the diagnosis of SGP in 20% of the LG MD families. None of the positive alpha-SG patients were deficient for any of the other three SG proteins, supporting the view that the SG complex fun ctions as a unit. DNA analysis for the four sarcoglycan genes showed that a lpha-SG mutations accounted for 47%, beta-SG for 16%, gamma-SG for 16% and delta-SG for 21% of the cases. SG abnormalities were observed in only 8.5% of patients with milder LGMD forms, but were present in 68% of patients wit h a severe Duchenne-like course. The relatively high frequency of SGP among Brazilian people with LGMD may be due to the disproportionally high freque ncy of African Brazilian SGP patients with the same mutation (particularly among LGMD2C and 2F patients), suggesting a founder effect. Consanguinity i s also common in our SGP families. (C) 1999 Elsevier Science B.V. All right s reserved.