title: A gene for dominant nonspecific X-linked mental retardation is located in Xq28.
abstract: A large family (MRX48) with a nonspecific X-linked mental retardation condition is described. An X-linked semidominant inheritance is suggested by the segregation in three generations of a moderate to severe mental retardation in seven males and by a milder intellectual impairment in two females, without any specific clinical, radiological, or biological feature. Two-point linkage analysis demonstrated significant linkage between the disorder and several markers in Xq28 (maximum LOD score [Zmax] = 2.71 at recombination fraction [theta] = 0); multipoint linkage analyses confirmed the significant linkage with a Zmax of 3.3 at theta = 0, at DXS1684. A recombination event observed with the flanking marker DXS8011 delineates a locus between this marker and the telomere. The approximate length of this locus is 8-9 cM, corresponding to 5.5-6 Mb. In an attempt to explain the variable intellectual impairment in females, we examined X-chromosome inactivation in all females of the family. Inactivation patterns in lymphocytes were random or moderately skewed, and no correlation between the phenotypic status and a specific inactivation pattern was observed. The interval of assignment noted in this family overlaps with five MRX loci previously reported in Xq28.
authors.affiliation: INSERM U129-ICGM, Faculté de Médecine Cochin, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: des Portes
authors.forename: P
authors.initials: P
authors.lastname: Billuart
authors.forename: A
authors.initials: A
authors.lastname: Carrié
authors.forename: L
authors.initials: L
authors.lastname: Bachner
authors.forename: T
authors.initials: T
authors.lastname: Bienvenu
authors.forename: M C
authors.initials: MC
authors.lastname: Vinet
authors.forename: C
authors.initials: C
authors.lastname: Beldjord
authors.forename: G
authors.initials: G
authors.lastname: Ponsot
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: J
authors.initials: J
authors.lastname: Boué
authors.forename: J
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000328:Adult; D000368:Aged; D002675:Child, Preschool; D002874:Chromosome Mapping; D004303:Dosage Compensation, Genetic; D005260:Female; D005602:France; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008126:Lod Score; D008297:Male; D011581:Psychological Tests; D011594:Psychometrics; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome
chemical_list: D005819:Genetic Markers