title: X inactivation testing for identifying a non-syndromic X-linked mental retardation gene.
abstract: The purpose of this study was to identify a gene causing non-syndromic X-linked mental retardation in an extended family, taking advantage of the X chromosome inactivation status of the females in order to determine their carrier state. X inactivation in the females was determined with the androgen receptor methylation assay; thereafter, the X chromosome was screened with evenly spaced polymorphic markers. Once initial linkage was identified, the region of interest was saturated with additional markers and the males were added to the analysis. Candidate genes were sequenced. Ten females showed skewed inactivation, while six revealed a normal inactivation pattern. A maximal lod score of 5.54 at θ = 0.00 was obtained with the marker DXS10151. Recombination events mapped the disease gene to a 17.4-Mb interval between the markers DXS10153 and DXS10157. Three candidate genes in the region were sequenced and a previously described missense mutation (P375L) was identified in the ACSL4/FACL4 gene. On the basis of the female X inactivation status, we have mapped and identified the causative mutation in a gene causing non-syndromic X-linked mental retardation.
authors.affiliation: The Danek Gartner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Hagith
authors.initials: H
authors.lastname: Yonath
authors.forename: Dina
authors.initials: D
authors.lastname: Marek-Yagel
authors.forename: Haike
authors.initials: H
authors.lastname: Resnik-Wolf
authors.forename: Almogit
authors.initials: A
authors.lastname: Abu-Horvitz
authors.forename: Hagit N
authors.initials: HN
authors.lastname: Baris
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Moshe
authors.initials: M
authors.lastname: Frydman
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
mesh_terms: D000293:Adolescent; D000328:Adult; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D049951:X Chromosome Inactivation
chemical_list: D005819:Genetic Markers