title: TM4SF2 gene involvement reconsidered in an XLMR family after neuropsychological assessment.
abstract: The TM4SF2 gene (localized at Xp11.4 between the loci DXS564 and DXS556) has been found to be mutated in one MRX family. In order to define the corresponding behavioral phenotype, global IQ and specific cognitive skills were assessed in seven males and three females of this family, independent of subject status. Mental retardation (MR) was mild in three patients and moderate in three others. Despite the broad variability of severity of MR, a cognitive profile specific to the MR in this family was documented. It was characterized by language disorder that was more marked in the articulatory component and spatial/verbal short-term memory dissociation with larger mnemonic span for spatial than for verbal cues. Linkage analysis was then performed on the basis of the cognitively determined status. Recombinations were observed with the loci DXS556 at Xp11.4 and DXS441 at Xq13.2 (maximum LOD score = 2.23 at theta = 0 for ALAS2). This localization region does not include the TM4SF2 gene that has been found mutated in both patients with MR and in one non-MR male subject of this family. The present results suggest two main hypotheses. First, TM4SF2 gene mutation could be involved in MR in this family, therefore representing accentuated intra familial phenotypic variability. Second, the structural particularity detected in the TM4SF2 gene might reflect a rare polymorphism rather than a pathogenic mutation, with the gene responsible for MR in this family being therefore more likely to be searched for in the pericentromeric region of the X chromosome.
authors.affiliation: Service de Génétique, INSERM 4316 CHU Bretonneau, Tours, France. m.gomot@chu-tours.fr
authors.forename: Marie
authors.initials: M
authors.lastname: Gomot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ronce
authors.forename: Sabine
authors.initials: S
authors.lastname: Dessay
authors.forename: Ramzi
authors.initials: R
authors.lastname: Zemni
authors.forename: Anne-Dominique
authors.initials: AD
authors.lastname: Ayrault
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Moizard
authors.forename: Annie
authors.initials: A
authors.lastname: Nivelon
authors.forename: Simone
authors.initials: S
authors.lastname: Gilgenkrantz
authors.forename: Julliette
authors.initials: J
authors.lastname: Dourlens
authors.forename: Vincent
authors.initials: V
authors.lastname: Des Portes
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
mesh_terms: D000328:Adult; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D059470:Tetraspanins
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C404405:TSPAN7 protein, human; D059470:Tetraspanins