X-linked mental retardation (MR) accounts for up to 20% of all patients with MR, and only about 20% of X-linked MR is due to fragile X syndrome. Patients' phenotypes and deletions indicate the presence of one or more MR loci in the Xp22.1-p21.3 region telomeric to the adrenal hypoplasia congenita locus. The purpose of the present study was to identify genes that mapped to this interval and were expressed in the central nervous system (CNS). In order to identify MR candidates genes within the MR critical region, we screened a human BAC library and a human X chromosome specific cosmid library with multiple sequence tag sites (STS) from this region by a combination of PCR and hybridization techniques. We generated contigs in this region by re-screening the genomic libraries with the end fragments of the BAC and cosmid clones. The expressed sequences in these genomic clones were identified by a genomic scanning method using brain cDNA libraries; full-length cDNAs were subsequently isolated and sequenced. In addition, we identified expressed sequence tags (ESTs), exons and genes in this region by searching genome databases. We have identified two genes in this region, which, by protein sequence database comparisons appear to be an aspartate aminotransferase and a serine/threonine protein phosphatase. Both genes are expressed in human fetal and adult brain cDNA libraries and both appear to map in the region telomeric to DXS28 in Xp22.1.

In conclusion, the Xp22.1-p21.3 MR critical region contains members of the aspartate aminotransferase and serine/threonine protein phosphatase gene families that are expressed in the CNS. These and other genes in this region will be analyzed for mutations in patients with isolated X-linked MR.