Genetic evidence for a novel gene(s) involved in urogenital development on10q26

Background. Although the frequent association between distal 10q monosomy a nd urogenital anomalies suggests the presence of a gene(s) for urogenital d evelopment on distal 10q, molecular deletion mapping has not been performed for the putative gene(s). In this study, we examined genotype-phenotype co rrelations in patients with distal 10q monosomy. Methods. This study consisted of six karyotypic males (cases 1 through 6) a nd four karyotypic females (cases 7 through 10) with 10q26 monosomy. Cases 3 through 5 and 7 through 10 had urinary anomalies such as vesicoureteral r eflux and hypoplastic kidney, and cases 1 through 6, 8, and 9 exhibited gen ital anomalies such as micropenis, hypospadias, cryptorchidism, and hypopla stic labia majora. Fluorescence in situ hybridization (FISH) for 10q telome re, whole chromosome 10 painting, and microsatellite analysis for 35 loci o n distal 10q were performed in cases 1 through 8. Results. FISH and whole chromosome painting confirmed distal 10q monosomy i n cases 1 through 8. Microsatellite analysis revealed that hemizygosity for the region distal to D10S186 was shared by cases with urinary anomalies an d that for the region distal to D10S1248 was common to cases with genital a nomalies. Furthermore, it was indicated that PAX2, GFRA1, and EMX2 on dista l 10q, in which the deletions could affect urinary and/or genital developme nt, were present in two copies in cases 1 through 8. Conclusions. The results suggest that a novel gene(s) for urinary developme nt and that for genital development reside in the approximately 20 cM regio n distal to D10S186 and in the approximately 10 cM region distal to D10S124 8, respectively, although it remains to be determined whether the two types of genes are identical or different.