GENETIC-HETEROGENEITY OF SEVERE CHILDHOOD AUTOSOMAL RECESSIVE MUSCULAR-DYSTROPHY WITH ADHALIN (50 KDA DYSTROPHY-ASSOCIATED GLYCOPROTEIN) DEFICIENCY

Severe autosomal recessive muscular dystrophy (SCARMD), McKusick n deg rees 253700, has been originally described in North-African population s, in which significant linkage has been established with DNA markers mapping to the proximal region of the long arm of chromosome 13, witho ut evidence for heterogeneity of the SCARMD locus in these populations . A striking feature of this disease is the isolated deficiency of adh alin, a sarcolemmal 50 kDa dystrophin-associated glycoprotein. We repo rt a non-inbred French family with a milder progressive form of muscul ar dystrophy affecting subjects of both sexes. The parents are not aff ected suggesting an autosomal recessive transmission. In 4 siblings di splaying mild to overt clinical signs of muscular dystrophy, serum cre atine kinase was high, and muscle specimens showed variable degree of necrosis-regeneration with little fibrosis. In the 4 cases adhalin was completely absent in muscle sections, whereas dystrophin and the othe r members of the dystrophin-associated protein complex were normal, ex cept for the 35 kDa dystrophin-associated glycoprotein which was decre ased as usually observed in SCARMD. Linkage and homogeneity analysis u sing 4 microsatellite markers of chromosome 13q that are linked to the North-African SCARMD locus were performed in this family. Results sho w that the morbid locus involved in this family does not map to the sa me region as the SCARMD locus. This second locus may be involved in sp oradic cases of muscular dystrophy with adhalin deficiency that have b een reported in Europe.