GENOMIC STRUCTURE OF A HUMAN HOLOCYTOCHROME C-TYPE SYNTHETASE GENE INXP22.3 AND MUTATION ANALYSIS IN PATIENTS WITH RETT-SYNDROME

The human holocytochrome c-type synthetase (HCCS) gene is located on X p22.3 and is one of the genes identified in a 450-Kb region deleted in the neurodevelopmental disorder microphthalmia with linear skin defec ts. Several other developmental disorders with or without a neurologic al phenotype have been linked to Xp22.3, This region of the X chromoso me was also found to be concordant in patients with Rett syndrome (RTT ) in previously performed exclusion mapping. Based on its chromosomal location and its role in the mitochondrial respiratory chain, we analy zed HCCS as a candidate gene for RTT, The genomic structure of this ge ne, which occupies an 11-Kb region and consists of seven exons, was de termined. All intron-exon boundaries were sequenced and primers were d esigned for polymerase chain reaction (PCR) amplification of each codi ng exon, PCR-amplified products from genomic DNA isolated from 20 RTT patients were screened for mutations using heteroduplex analysis, No m utations were detected. The genomic characterization of this gene will allow us to perform mutation analysis for other inherited disorders l inked to this region. Am. J, Med, Genet. 78:179-181, 1998. (C) 1998 Wi ley-Liss, Inc.