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 id entified, and permanent (Epstein Barr virus transformed) cell lines we re established from members of four of the families. 2. A genetic link age 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) ge ne. 3. The segregation of the markers in two of the five families was compatible with the disease-causing locus being located in this same r egion. In one family the pattern of segregation clearly excludes the c ausative gene from this region. In one of the remaining two families t he analysis was inconclusive because the markers were not informative. In the fifth family the possibility of two concurrent neuromuscular d iseases 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 pos sibility of non-allelic heterogeneity for the spinal muscular atrophy gene is discussed.