A functional tetranucleotide (AAAT) polymorphism in an Alu element in the NF1 gene is associated with mental retardation

作者：Vedrine Sylviane Marouillat; Vourc'h Patrick; Tabagh Refaat; Mignon Laurence; Hoefflin Saskya; Cherpi Antar Catherine; Mbarek Olivier; Paubel Agathe; Moraine Claude; Raynaud Martine; Andres Christian R^*

来源：Neuroscience Letters, 2011, 491(2): 118-121.

DOI：10.1016/j.neulet.2011.01.019

• Non-syndromic mental retardation
• Association study
• Neurofibromatosis type 1
• Non-denaturing HPLC
• CAT

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 (chi(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.

• 出版日期2011-3-17