title: A functional tetranucleotide (AAAT) polymorphism in an Alu element in the NF1 gene is associated with mental retardation.
abstract: Mental retardation (MR) is frequent in neurofibromatosis type 1 (NF1). Allele 5 of a tetranucleotide polymorphism in an Alu element (GXAlu) localized in intron 27b of the NF1 gene has previously been associated with autism. We considered that the microsatellite GXAlu could also represent a risk factor in MR without autism. We developed a rapid method for genotyping by non-denaturing HPLC and assayed the allelic variation of GXAlu marker on in vitro gene expression in Cos-7 cells. A French population of 157 individuals (68 non syndromic non familial MR (NS-MR) patients diagnosed in the University Hospital of Tours; 89 controls) was tested in a case-control assay. We observed a significant association (χ(2)=7.96; p=0.005) between alu4 carriers (7 AAAT repeats) and MR (OR: 7.86; 95% C.I.: 2.13-28.9). The relative in vitro expression of a reporter gene encoding chloramphenicol acetyl transferase (CAT) was higher for alu4 and alu5, suggesting a regulation effect for these alleles on gene expression in vivo. Our results showed an association with a polymorphism regulating the NF1 gene or other genes during brain development.
authors.affiliation: UMR INSERM U930, CNRS ERL 3106, Université François Rabelais de Tours, Tours, France.
authors.forename: Sylviane Marouillat
authors.initials: SM
authors.lastname: Védrine
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Refaat
authors.initials: R
authors.lastname: Tabagh
authors.forename: Laurence
authors.initials: L
authors.lastname: Mignon
authors.forename: Saskya
authors.initials: S
authors.lastname: Höfflin
authors.forename: Catherine
authors.initials: C
authors.lastname: Cherpi-Antar
authors.forename: Olivier
authors.initials: O
authors.lastname: Mbarek
authors.forename: Agathe
authors.initials: A
authors.lastname: Paubel
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Martine
authors.initials: M
authors.lastname: Raynaud
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
mesh_terms: D000293:Adolescent; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016514:Genes, Neurofibromatosis 1; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction