A new submicroscopic deletion that refines the 9p region for sex reversal

Male to female sex reversal has been described in patients with deletions o f chromosome 9p, and a region critical for sex reversal has been localized to p24.3, at the tip of the chromosome (TD9). It was proposed that the sex reversal may arise by haploinsufficiency for a gene localized to the minimu m deletion. The 9p24.3 genes DMRT1 and DMRT2 are the favorite TD9 candidate s to date, in virtue of their sequence similarity to doublesex and mab-3 se xual regulators in Drosophila and Caenorhabditis elegans, respectively. The hypothesis of sex reversal by combined haploinsufficiency for the two gene s was put forward to explain the lack of mutations in either gene in XY sex -reversed females, Here we describe a XY sex-reversed patient carrying a no vel 9p deletion that extends over less than 700 kb of genomic DNA. This reg ion defines the smallest interval for sex reversal found to date. DMRT1 and DMRT2 map outside this region, Our data do not support the hypothesis of c ombined haploinsufficiency for DMRT1 and DMRT2. Nevertheless, DMRT1 localiz es very close to the deletion breakpoint and has a pattern of expression co mpatible with a role in sex determination, It therefore remains a candidate gene for 9p sex reversal. (C) 2000 Academic Press.