The definition of the Y chromosome growth-control gene (GCY) critical region: relevance of terminal and interstitial deletions.

Deletions of the long arm of the Y chromosome are often associated with short stature and infertility. Initial mapping assignments to narrow down the localization of the Y chromosome growth-control gene, GCY, were based on molecular analysis of patients carrying a 46,XYq- karyotype as defined by classic karyotyping. Two non-overlapping critical regions for GCY were defined. To determine whether one or both of these regions contained GCY, adult patients with monocentric Yq- chromosomes were reinvestigated in detail. Fluorescence in situ hybridization (FISH) analysis showed that all patients previously defined as having a pure 46,XYq- karyotype were in fact mosaics, with cells containing an idic(Y) or ring(Y) chromosome in association with 45,X cells. This excluded patients with terminal deletions as reliable subjects of study to locate the stature gene on Yq. In contrast, detailed molecular deletion analysis of patients who had interstitial deletions of the long arm of the Y chromosome pointed unequivocally to a single region next to the centromere that had a possible impact on growth. No functional gene has been identified in this region.