FISH-DELETION MAPPING DEFINES A 270-KB SHORT STATURE CRITICAL INTERVAL IN THE PSEUDOAUTOSOMAL REGION PAR1 ON HUMAN SEX-CHROMOSOMES

Deletions of the pseudoautosomal region (PAR1) of the sex chromosomes have recently been discovered in individuals with short stature, and a minimal common deletion region of 700 kb within PAR1 has subsequently been defined, We have cloned this entire region, which is bounded by the Xp/Yp telomere, as an overlapping cosmid contig. In the present st udy, we have used fluorescence in situ hybridization (FISH) to study f our patients with X-chromosomal rearrangements, two with normal height and two with short stature. Genotype-phenotype correlations have narr owed down the the critical ''short stature interval'' to a 270-kb regi on containing the gene with an important role in growth. A minimal til ing path of 6-8 cosmids bridging this interval is now available for in terphase and metaphase FISH and provides a valuable tool for diagnosti c investigations of patients with idiopathic short stature.