ASSESSMENT OF NONALLELIC GENETIC-HETEROGENEITY OF CHRONIC (TYPE-II AND TYPE-III) SPINAL MUSCULAR-ATROPHY

We have previously reported the mapping of the chronic (type II/interm ediate and type III/mild/Kugelberg-Welander) form of the childhood-ons et spinal muscular atrophies (SMA) to chromosome 5q11.2-13.3, with evi dence for nonallelic genetic heterogeneity within a small sample of se ven families [Brzustowicz et al., Nature 1990;344:540-541]. We now rep ort the results of linkage analysis and heterogeneity testing on a set of 38 families with chronic SMA. Significant evidence for nonallelic heterogeneity was detected among these families, with the predominant locus for chronic SMA mapping to a 0.51-cM region on 5q, between the l oci D5S6 and MAP1B. The estimated proportion of linked families, a, wa s 0.91, with a 2.3-unit support interval of 0.75 to 0.98. The indicati on that some families diagnosed nosed with chronic SMA are not linked to chromosome 5q must be considered in strategies to map the SMA locus . The relevance of these findings to acute SMA (SMA type I, severe, We rdnig-Hoffmann disease) is still unknown.