Genetic Study of Two Candidate Genes, FBXO25 and ARHGEF10, in Autism Spectrum Disorders.

• Main Authors: Wan-Rou Chen, 陳婉柔
• Other Authors: Chia-Hsiang Chen
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/26818068096871531634

碩士 === 慈濟大學 === 分子生物暨人類遺傳學系碩士班 === 100 === Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopment disorders, it can be diagnosed before three years of age, the syndromes of ASD are defined by the damage of social interaction, abnormal development of speech and language, and highly restricted interests and stereotyped behavior. Previous studies showed that ASD are highly heritable, however, the disease causing genes are poorly known. We recently reported that using Array Comparative Genomic Hybridization analysis (array CGH), a boy with ASD who had a terminal deletion at the short arm of chromosome 8, was detected.The deletion region contains 23 genes. To further elucidate which genes might be associated with ASD, we investigated two genes in this study, i.e. F-box protein 25 (FBXO25) and the Rho guanine nucleotide exchange factor 10 (ARHGEF10). To investigate whether the FBXO25 and the ARHGEF10 are associated with ASD, we set out to screen mutations of these two genes in ASD. We used PCR-based direct sequencing to screen mutations at all the exonic regions of these two genes in 360 ASD patients and 400 controls. We identified a missense mutation R38H in the FBXO25 in one patient. In ARHGEF10 gene, we identified several missense mutations, including D96N, G118C, G187S, E189V, R275H, V700I, T970M, T1173S, I1241F, Y1282C, and R1320S. Five mutations, G118C, G187S, E189V, T970M and Y1282C, were only found in patients, but not in controls. Computer programs of PolyPhen and SIFT predict that G118C, R275H and T1173S mutations of ARHGEF10 gene are probably damaging. And only in SIFT, E189V was probably damaging. In ARHGEF10, E189V mutation had significant difference of genotype frequency and allele frequency of case-control analysis (genotype frequency, p=0.03, allele frequency, p=0.04). These mutations might be result in increased risk to ASD.