Linkage and apparent heterogeneity in proximal spinal muscular atrophies

Linkage studies with 9 highly informative DNA markers on the long arm of chromosome 5 were performed in 12 multiplex families (29 patients) with spinal muscular atrophy (SMA) from The Netherlands. The results of the linkage analysis were compatible with localization of a major SMA gene in the chromosomal region 5q12-13. By minimum recombinant analysis the most likely position of the SMA locus was between loci D5S6/D5S125 and D5S112/MAP1B, which is in agreement with several linkage studies from other countries. In four families, however, more than one crossover between SMA and a flanking DNA marker appeared, and in one family the observed hybridization phenotype for the markers closely flanking the SMA locus was identical for an unaffected individual and for his two affected sibs with SMA type III. For this latter family, among several explanations the most likely are either the presence of a double crossover or linkage heterogeneity.