Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity

Abstract

Marked deficiency of muscle adhalin, a 50 kDa sarcolemmal dystrophin-associated glycoprotein^1–3, has been reported in severe childhood autosomal recessive muscular dystrophy (SCARMD)⁴. This is a Duchenne-like disease affecting both males and females first described in Tunisian families^5,6. Adhalin deficiency has been found in SCARMD patients from North Africa^4,7,8 Europe⁹, Brazil¹⁰, Japan^11,12 and North America (SLR & KPC, unpublished data). The disease was initially linked to an unidentified gene on chromosome 13 in families from North Africa^7,13, and to the adhalin gene itself on chromosome 17q in one French family in which missense mutations were identified¹⁴. Thus there are two kinds of myopathies with adhalin deficiency: one with a primary defect of adhalin (primary adhalinopathies), and one in which absence of adhalin is secondary to a separate gene defect on chromosome 13. We have examined the importance of primary adhalinopathies among myopathies with adhalin deficiency, and describe several additional mutations (null and missense) in the adhalin gene in 10 new families from Europe and North Africa. Disease severity varies in age of onset and rate of progression, and patients with null mutations are the most severely affected.