Li Hong, Yamagata Takanori, Mori Masato, Momoi Mariko Y
Department of Pediatrics, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
Brain Dev. 2005 Apr;27(3):207-10. doi: 10.1016/j.braindev.2004.06.002.
We analyzed the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, for a possible causative mutation in autism. FOXP2 was reported to be mutated in patients with a severe speech and language disorder. FOXP2 was located on chromosome 7q31, which is one of the loci involved in autism. Autism and specific language impairment share some of their clinical phenotypes. In addition, FOXP2 was expressed abundantly in the brain. We screened all of the exons of FOXP2 for causative mutations in 53 Japanese autistic patients using denaturing high-performance liquid chromatography and direct sequencing. A delCAA in exon 5 causing one glutamine deletion in the first polyglutamine tract was detected in four patients and in 2 of 50 control individuals. The frequency of the TT allele with the G to T base change in intron 15 was significantly high in the autistic population. The other base changes included one silent base change (A569G) in exon 5 and three in introns. Our results may suggest a relationship between autism and the FOXP2 gene or a gene located nearby.
我们分析了FOXP2基因，该基因编码一种含有多聚谷氨酰胺序列和叉头DNA结合域的假定转录因子，以寻找自闭症可能的致病突变。据报道，FOXP2在患有严重言语和语言障碍的患者中发生了突变。FOXP2位于7号染色体的q31区域，这是与自闭症相关的位点之一。自闭症和特定语言障碍有一些共同的临床表型。此外，FOXP2在大脑中大量表达。我们使用变性高效液相色谱法和直接测序法，对53名日本自闭症患者的FOXP2所有外显子进行了致病突变筛查。在4名患者以及50名对照个体中的2名中，检测到外显子5中的delCAA，该突变导致第一个多聚谷氨酰胺序列中的一个谷氨酰胺缺失。自闭症群体中，内含子15中发生G到T碱基变化的TT等位基因频率显著较高。其他碱基变化包括外显子5中的一个沉默碱基变化（A569G）以及内含子中的三个碱基变化。我们的结果可能提示自闭症与FOXP2基因或其附近的某个基因之间存在关联。
