Warburton P, Baird G, Chen W, Morris K, Jacobs B W, Hodgson S, Docherty Z
Division of Medical and Molecular Genetics, Guy's Hospital, London,
Am J Med Genet. 2000 Apr 3;96(2):228-34. doi: 10.1002/(sici)1096-8628(20000403)96:2<228::aid-ajmg20>3.0.co;2-g.
Childhood autism is characterised by impairments in communication and reciprocal social interaction together with restricted/stereotyped interests, which are evident before 3 years of age. Specific developmental disorders of speech and language (SDDSL) are characterised by impairment in the development of expressive and/or receptive language skills which is not associated with intellectual, sensory, physical, or neurological impairment. Family and twin studies indicate a substantial genetic component in the aetiology of both disorders. They also reveal increased rates of SDDSL in relatives of autistic individuals, suggesting that this phenotype can represent one manifestation of the genetic liability for autism. Modelling of the recurrence risk for autism and milder phenotypes, such as SDDSL, suggest that three or four epistatic loci may be aetiologically involved. A recently published linkage study of an exceptional family with an apparently dominantly inherited SDDSL implicated chromosome band 7q31 as the site of the putative susceptibility locus (SPCH1). This region of chromosome 7 also shows strong linkage in multiplex families with autism. We present two individuals (one has autism, the other SDDSL) with different, apparently balanced chromosome rearrangements involving a breakpoint at 7q31.3. Fluorescence in situ hybridisation was used to localise the breakpoints to an approximately 1 cM interval between CFTR and D7S643. Our findings may be of interest and relevance to the genetic aetiology of autism, and helpful in the search for susceptibility loci for SDDSL and autism. Am. J. Med. Genet. (Neuropsychiatr. Genet. ) 96:228-234, 2000.
儿童自闭症的特征是在3岁之前出现沟通和双向社交互动障碍，以及兴趣受限/刻板。特定性言语和语言发育障碍（SDDSL）的特征是表达性和/或接受性语言技能发育受损，且与智力、感官、身体或神经损伤无关。家族和双胞胎研究表明，这两种疾病的病因都有很大的遗传因素。研究还发现自闭症患者亲属中SDDSL的发病率增加，这表明这种表型可能是自闭症遗传易感性的一种表现。对自闭症和较轻表型（如SDDSL）复发风险的建模表明，可能有三到四个上位基因座在病因上起作用。最近发表的一项对一个具有明显显性遗传SDDSL的特殊家庭的连锁研究表明，染色体带7q31是假定的易感基因座（SPCH1）所在位置。7号染色体的这个区域在自闭症的多个家族中也显示出很强的连锁性。我们报告了两个个体（一个患有自闭症，另一个患有SDDSL），他们有不同的、明显平衡的染色体重排，断点位于7q31.3。荧光原位杂交被用于将断点定位到CFTR和D7S643之间大约1厘摩的区间。我们的发现可能与自闭症的遗传病因相关，有助于寻找SDDSL和自闭症的易感基因座。《美国医学遗传学杂志》（神经精神遗传学）96:228 - 234，2000年。
