Characterization of ARHGEF6, a guanine nucleotide exchange factor for Rho GTPases and a candidate gene for X-linked mental retardation: mutation screening in Börjeson-Forssman-Lehmann syndrome and MRX27.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a syndromic X-linked mental retardation that has been mapped by linkage to Xq26-q27. A nonsyndromic mental retardation family, MRX27, has also been localized to a region of the X chromosome overlapping Xq26-q27. The gene for ARHGEF6 (also known as alphaPIX or Cool-2), a newly identified guanine nucleotide exchange factor, was identified as a potential candidate XLMR gene, due to its location within the BFLS and MRX27 critical regions and its function in the regulation of PAK3 (a known MRX gene). The full coding sequence and genomic structure of the gene for ARHGEF6 was established in silico, based on available genomic, EST, and cDNA sequence information. Mutation analysis in BFLS- and MRX27-affected individuals was carried out. No mutations were found in two BFLS families or MRX27. Although ARHGEF6 is unlikely to be the gene responsible for either BFLS or MRX27, it remains a prime candidate for nonspecific or syndromic mental retardation linked to Xq26.