Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q.

Proximal spinal muscular atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). These different clinical forms have previously been attributed to either genetic heterogeneity or variable expression of different mutations at the same locus. Research has been hindered because the underlying biochemical defect is unknown, and there are insufficient large pedigrees with the most common and severe form (type I) available for study. Therefore, we have undertaken a genetic linkage analysis of the chronic forms of the disease (types II and III) as an initial step towards the ultimate goal of characterizing the gene(s) responsible for all three types. We report here the assignment of the locus for the chronic forms to the long arm of chromosome 5 (5q12-q14), with the anonymous DNA marker D5S39, in 24 multiplex families of distinct ethnic origin. Furthermore, no evidence for genetic heterogeneity was found for types II and III in our study, suggesting that these two forms are allelic disorders.