RT Journal Article
SR Electronic
T1 Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D).
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 470
OP 475
DO 10.1136/jmg.34.6.470
VO 34
IS 6
A1 A Carrié
A1 F Piccolo
A1 F Leturcq
A1 C de Toma
A1 K Azibi
A1 C Beldjord
A1 J M Vallat
A1 L Merlini
A1 T Voit
A1 C Sewry
A1 J A Urtizberea
A1 N Romero
A1 F M Tomé
A1 M Fardeau
A1 Y Sunada
A1 K P Campbell
A1 J C Kaplan
A1 M Jeanpierre
YR 1997
UL http://jmg.bmj.com/content/34/6/470.abstract
AB Sarcoglycanopathies are a genetically heterogeneous group of autosomal recessive muscular dystrophies in which the primary defect may reside in any of the genes coding for the different partners of the sarcolemmal sarcoglycan (SG) complex: the alpha-SG (LGMD2D at 17q21.2), the beta-SG (LGMD2E at 4q12), the gamma-SG (LGMD2C at 13q12), and the delta-SG (LGMD2F at 5q33). We report a series of 20 new unrelated families with 14 different mutations in the alpha-SG gene. Along with the mutations that we previously reported this brings our cohort of patients with alpha-sarcoglycanopathy to a total of 31 unrelated patients, carrying 25 different mutations. The missense mutations reside in the extracellular domain of the protein. Five of 15 missense mutations, carried by unrelated subjects on different haplotype backgrounds and of widespread geographical origins, account for 58% of the mutated chromosomes, with a striking prevalence of the R77C substitution (32%). The severity of the disease varies strikingly and correlates at least in part with the amount of residual protein and the type of mutation. The recurrent R284C substitution is associated with a benign disease course.