FISH-deletion mapping defines a 270-kb short stature critical interval in the pseudoautosomal region PAR1 on human sex chromosomes

Abstract

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 study, we have used fluorescence in situ hybridization (FISH) to study four patients with X-chromosomal rearrangements, two with normal height and two with short stature. Genotype-phenotype correlations have narrowed down the the critical “short stature interval” to a 270-kb region containing the gene with an important role in growth. A minimal tiling path of 6–8 cosmids bridging this interval is now available for interphase and metaphase FISH and provides a valuable tool for diagnostic investigations of patients with idiopathic short stature.