The use of chromosome 5q markers for confirming the diagnosis of proximal spinal muscular atrophy.

1. Five Brazilian families referred to us with a probable diagnosis of chronic proximal spinal muscular atrophy (Kugelberg-Welander) were identified, and permanent (Epstein Barr virus transformed) cell lines were established from members of four of the families. 2. A genetic linkage study was carried out on 70 individuals using nine polymorphic DNA markers (eight RFLP and one microsatellite) from chromosome 5q11.2-13.3 which have been shown to flank the spinal muscular atrophy (SMA) gene. 3. The segregation of the markers in two of the five families was compatible with the disease-causing locus being located in this same region. In one family the pattern of segregation clearly excludes the causative gene from this region. In one of the remaining two families the analysis was inconclusive because the markers were not informative. In the fifth family the possibility of two concurrent neuromuscular diseases did not permit a definite conclusion. 4. These results further support the location of the major SMA gene at 5q11.2-13.3. 5. The possibility of non-allelic heterogeneity for the spinal muscular atrophy gene is discussed.