Exon Detection Of The FMR1Gene In Mentally Retarded Population In Qinba Region

Mental Retardation is a kind of Neurological and psychiatric disease, which seriously affects the children’s physical and psychological health. Hypophrenia and defect of social adaptation ability are main parts of the symptom. Fragile X syndrome is a kind of common hereditary MR, which is caused by the abnormality of FMRI gene. The pathogenesis of MR which is related to FMR1gene is still unknown. Numerous studies showed that excessive amplification of (CGG) n repeats in untranslated region of FMR1gene resulted in abnormal methylation of CpG island,which finally caused gene silencing. Other reports showed that MR can be caused by abnormal methylation of CpG island alone, even the (CGG) n repeats is within the normal range. Also a few reports showed that the point mutations can laed to this disease. In order to research the inherited pathogenic factor of mental retardation in Qinba area, our research group had detected (CGG) n repeats and the degree of methylation of CpG island in FMRI gene within MR patients in this area, which showed that there were3MR patients with abnormal methylation of CpG island but without abnormal CGG repeats.In order to further study the relation between MR and point mutations in FMR1gene,17exons in FMRI gene coding region was detected by PCR-SSCP technology in410MR patient in Qinba area.The result showed that there was a base substitution cDNA414G>A,which was discovered in a DNA sample of female MR patient. This mutation site was the third base of codon138in the coding area of FMRI gene, which was synonymous change p.Arg138Arg. To find out whether this mutation influenced the alternative splicing of mRNA or not, cDNA sequence of FMR1gene was analyzed as well, through RT-PCR combined with DNA sequencing. The result showed that there was abnormal alternative splicing in exon12of FMR1gene, which could contribute to this patient suffering from MR.