Human Molecular Genetics Advance Access published online on May 11, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi186
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1 Dept. of Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium
* To whom correspondence should be addressed. X-linked ichthyosis (XLI) is often associated with a recurrent microdeletion at Xp22.31 due to non-allelic homologous recombination (NAHR) between the CRI-S232 low-copy repeat regions flanking the STS gene. The clinical features of these patients may include mental retardation (MR) and the VCX-A gene has been proposed as the candidate MR gene. Analysis of DNA from 4 XLI patients with MR by array-CGH on a 150 kb resolution X chromosome-specific array revealed a 1.5 Mb interstitial microdeletion with breakpoints in the CRI-S232 repeat sequences, each of which harbors a VCX gene. We demonstrate that the recombination sites in all four cases are situated in the 1 kb repeat unit 2 (RU2) region present at the 3' ends of the VCX-A and VCX-B genes thereby deleting VCX-A and VCX-B1 but not VCX-B and VCX-C. Array-CGH with DNA of an XLI patient with MR and an inherited t(X;Y)(p22.31;q11.2) showed an Xpter deletion of 8.0 Mb resulting in the deletion of all four VCX genes and duplication of both VCY homologs. These data confirm the role of VCX-A in the occurrence of MR in XLI patients. Moreover, we propose a VCX/Y teamwork-dependent mechanism for the incidence of mental impairment in XLI patients.
Received March 16, 2005
Revised May 4, 2005
Accepted May 4, 2005
Article
Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis
2 Human Genome Laboratory, Dept. of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Leuven, Belgium
3 Microarray Facility, VIB, Leuven, Belgium
4 Human Genome Laboratory, Dept. of Human Genetics, VIB, Gasthuisberg O&N6, Herestraat 49, P.O. box 602, B-3000 Leuven, Belgium
Guy Froyen, E-mail: guy.froyen{at}med.kuleuven.ac.be
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