LINKAGE MAPPING OF THE SPINAL MUSCULAR-ATROPHY GENE

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder resulting in loss of motor neurons. We have performed linkage analysi s on a panel of families using nine markers that are closely linked to the SMA gene. The highest lod score was obtained with the marker D5S3 51 (Z(max) = 10.04 at theta = 0 excluding two unlinked families, and Z (max) = 8.77 at theta = 0.007 with all families). One type III family did not show linkage to the 5q13 markers, and in one type I consanguin eous family the affected individual did not show homozygosity except f or the marker D5S435. Three recombinants were identified with the clos est centromeric marker, D5S435, which position the gene telomeric of t his marker. These recombinants will facilitate finer mapping of the lo cation of the SMA gene. Lastly, two families provide strong evidence f or a remarkable variability in presentation of the SMA phenotype, with the age at onset in one family varying from 17 months to 13 years.