LINKAGE ANALYSIS OF THE NAIL-PATELLA SYNDROME

Nail-patella syndrome (NPS) is an autosomal dominant disorder characte rized by dysplasia of nails and patella, decreased mobility of the elb ow, iliac horns, and, in some cases, nephropathy. The disorder has bee n mapped to the long arm of chromosome 9, but the precise localization and identity of the NPS gene are unknown. Linkage analysis in three N PS families, using highly informative dinucleotide repeat polymorphism s on 9q33-q34, confirmed linkage of NPS to this chromosome. Recombinat ions were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric mar kers D9S64 and D9S66, in one of the families. Haplotype analysis sugge sted an additional recombination between NPS and the argininosuccinate synthetase (ASS) gene. These results localize the NPS gene to an inte rval on 9q34.1, distal to D9S60 and proximal to ASS, comprising a gene tic distance of similar to 9 cM. This represents a significant refinem ent in the localization of the NPS gene.