UHX1 AND PCTK1 - PRECISE CHARACTERIZATION AND LOCALIZATION WITHIN A GENE-RICH REGION IN XP11.23 AND EVALUATION AS CANDIDATE GENES FOR RETINAL DISEASES MAPPED TO XP21.1-P11.2

The gene for ubiquitin hydrolase on the X chromosome (UHX1), cloned an d mapped to Xp21.2-p11.2, is a candidate gene for retinal diseases. We used fine mapping techniques to localise UHX1 between markers DXS1266 and DXS337, where congenital stationary night blindness (XICSNB) and retinitis pigmentosa type 2 (RP2) are also located. Reevaluation of th e UHX1 gene structure demonstrated five new exons, for a total of 21 e xons and a predicted protein product of 963 amino acids. Evaluation of patients revealed no UHX1 mutations using SSCP (10 CSNB1 and 20 XLRP) or deletion screening with cDNA hybridisation (13 CSNB1 and 43 XLRP). Likewise, no aberrations were found in the nearby PCTAIRE1 (PCTK1) ge ne in 13 CSNB1 and 43 XLRP patients by deletion screening. Thus mutati ons of UHX1, and probably PCTK1, do not appear to cause common X-linke d eye diseases. UHX1's role in patients with mental retardation may be appropriate for further investigations into UHX1 function.