LOCALIZATION OF THE GENE FOR A DOMINANT CONGENITAL SPINAL MUSCULAR-ATROPHY PREDOMINANTLY AFFECTING THE LOWER-LIMBS TO CHROMOSOME 12Q23-Q24

Spinal muscular atrophies are a heterogeneous group of disorders. They differ in time of onset, clinical presentation, progression, severity and mode of inheritance. In 1985 a Dutch family was described with a dominant, nonprogressive spinal muscular atrophy presenting at birth w ith arthrogryposis (MIM 600175). Linkage analysis was performed in thi s family. After having excluded the loci for Werdnig-Hoffmann's diseas e and for dominant distal spinal muscular atrophy with upper limb pred ominance, we were able to localise the gene to a 10 cM interval betwee n the markers D12S78 and D12S1646 on chromosome 12q23-q24. Recently, d ominant scapuloperoneal spinal muscular atrophy has been localised to an overlapping interval. However, the clinical appearances of scapulop eroneal spinal muscular atrophy and the present disorder make allelism unlikely. In 1994, a second Dutch family with a disorder similar to t he present one was described. We excluded linkage to markers of the 12 q23-q24 region in this family and thereby proved genetic heterogeneity of this type of dominant, congenital and nonprogressive spinal muscul ar atrophy.