GENOMIC REARRANGEMENTS IN CHILDHOOD SPINAL MUSCULAR-ATROPHY - LINKAGEDISEQUILIBRIUM WITH A NULL ALLELE

Autosomal recessive childhood onset spinal muscular atrophy has been m apped to chromosome 5q13. We report the analysis of a polymorphic micr osatellite which shows linkage disequilibrium with the disease. The li nkage disequilibrium is observed with a null allele which is seen as t he non-inheritance of alleles from one or both parents. The inheritanc e of a null allele was observed in 26 out of 36 (72%) informative chil dhood onset spinal muscular atrophy (SMA) families tested, of all type s of severity and from a variety of ethnic backgrounds. In seven famil ies segregating for the severe Werdnig-Hoffmann or SIMA type I, no all eles were inherited from either parent using this microsatellite. This null allele may represent a deletion which is either closely associat ed with, or causes, the disease.