Department of Pediatrics, UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Hum Genet. 2010 Aug;128(2):155-64. doi: 10.1007/s00439-010-0839-y. Epub 2010 May 25.
Previous research has suggested that individuals with constitutional hemizygosity of 18q have a higher risk of autistic-like behaviors. We sought to identify genomic factors located on chromosome 18 as well as other loci that correlate with autistic behaviors. One hundred and five individuals with 18q- were assessed by high-resolution oligo aCGH and by parental ratings of behavior on the Gilliam Autism Rating Scale. Forty-five individuals (43%) had scores within the "possibly" or "very likely" categories of risk for an autism diagnosis. We searched for genetic determinants of autism by (1) identifying additional chromosome copy number changes (2) Identifying common regions of hemizygosity on 18q, and (3) evaluating four regions containing candidate genes located on 18q (MBD1, TCF4, NETO1, FBXO15). Three individuals with a "very likely" probability of autism had a captured 17p telomere in addition to the 18q deletion suggesting a possible synergy between hemizygosity of 18q and trigosity of 17p. In addition, two of the individuals with an 18q deletion and a "very likely" probability of autism rating had a duplication of the entire short arm of chromosome 18. Although no common region of hemizygosity on 18q was identified, analysis of four regions containing candidate genes suggested that individuals were significantly more likely to exhibit autistic-like behaviors if their region of hemizygosity included TCF4, NETO1, and FBXO15 than if they had any other combination of hemizygosity of the candidate genes. Taken together, these findings identify several new potential candidate genes or regions for autistic behaviors.
先前的研究表明，18q 单体型缺失的个体具有更高的自闭症样行为风险。我们试图确定位于 18 号染色体上以及与自闭症行为相关的其他基因座上的基因组因素。105 名 18q-个体接受了高分辨率寡核苷酸 aCGH 和 Gilliam 自闭症评定量表的父母行为评定。45 名个体（43%）的评分处于自闭症诊断的“可能”或“很可能”风险类别。我们通过以下方法寻找自闭症的遗传决定因素：（1）确定额外的染色体拷贝数变化；（2）确定 18q 上常见的单体型缺失区域；（3）评估位于 18q 上的四个候选基因区域（MBD1、TCF4、NETO1、FBXO15）。三名患有“很可能”自闭症的个体除了 18q 缺失外，还存在捕获的 17p 端粒，这表明 18q 单体型缺失和 17p 三体性之间可能存在协同作用。此外，两名患有 18q 缺失和“很可能”自闭症评分的个体存在整个 18 号染色体短臂的重复。尽管未发现 18q 上常见的单体型缺失区域，但对包含候选基因的四个区域的分析表明，如果个体的单体型缺失区域包含 TCF4、NETO1 和 FBXO15，则其表现出自闭症样行为的可能性显著高于其他候选基因的任何组合。总之，这些发现确定了几个新的潜在候选基因或自闭症行为区域。
