Milner Katja M, Craig Ellen E, Thompson Russell J, Veltman Marijcke W M, Thomas N Simon, Roberts Sian, Bellamy Margaret, Curran Sarah R, Sporikou Caroline M J, Bolton Patrick F
Child & Adolescent Psychiatry Department & MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
J Child Psychol Psychiatry. 2005 Oct;46(10):1089-96. doi: 10.1111/j.1469-7610.2005.01520.x.
Studies of chromosome 15 abnormality have implicated over-expression of paternally imprinted genes in the 15q11-13 region in the aetiology of autism. To test this hypothesis we compared individuals with Prader-Willi syndrome (PWS) due to uniparental disomy (UPD--where paternally imprinted genes are over-expressed) to individuals with the 15q11-13 deletion form of the syndrome (where paternally imprinted genes are not over-expressed). We also tested reports that PWS cases due to the larger type I (TI) form of deletion show differences to cases with the smaller type II (TII) deletion.
Ninety-six individuals with PWS were recruited from genetic centres and the PWS association. Forty-nine individuals were confirmed as having maternal UPD of chromosome 15 and were age and sex matched to 47 individuals with a deletion involving 15q11-13 (32 had the shorter (T II) deletion, and 14 had the longer (TI) deletion). Behavioural assessments were carried out blind to genetic status, using the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview (ADI), the Autism Screening Questionnaire (ASQ), the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), the Vineland Adaptive Behaviour Scales (VABS), and measurements of intellectual ability, including the Wechsler and Mullen Scales and Raven's Matrices.
UPD cases exhibited significantly more autistic-like impairments in reciprocal social interaction on questionnaire, interview and standardised observational measures. Comparison of TI and TII deletion cases revealed few differences, but ability levels tended to be lower in the TI deletion cases.
Findings from a large study comparing deletion and UPD forms of Prader-Willi syndrome were consistent with other evidence in indicating that paternally imprinted genes in the 15q11-13 region constitute a genetic risk factor for aspects of autistic symptomatology. These genes may therefore play a role in the aetiology of autism. By contrast with another report, there was no clear-cut relationship between the size of the deletion and the form of cognitive and behavioural phenotype.
对15号染色体异常的研究表明，15q11 - 13区域父源印记基因的过表达与自闭症的病因有关。为了验证这一假设，我们将因单亲二体性（UPD，父源印记基因在此情况下过表达）导致普拉德 - 威利综合征（PWS）的个体与因15q11 - 13缺失型综合征（父源印记基因在此情况下不过表达）的个体进行了比较。我们还检验了以下报告，即因较大的I型（TI）缺失形式导致的PWS病例与较小的II型（TII）缺失病例存在差异。
从遗传中心和普拉德 - 威利综合征协会招募了96名患有普拉德 - 威利综合征的个体。49名个体被确认为15号染色体母源单亲二体性，在年龄和性别上与47名涉及15q11 - 13缺失的个体相匹配（32名有较短的（TII）缺失，14名有较长的（TI）缺失）。在对遗传状态不知情的情况下进行行为评估，使用自闭症诊断观察量表（ADOS）、自闭症诊断访谈（ADI）、自闭症筛查问卷（ASQ）、儿童耶鲁 - 布朗强迫症量表（CY - BOCS）、文兰适应行为量表（VABS）以及智力能力测量，包括韦氏和穆伦量表以及瑞文推理测验。
在问卷、访谈和标准化观察测量中，UPD病例在相互社交互动方面表现出明显更多的自闭症样损害。TI和TII缺失病例的比较显示差异较少，但TI缺失病例的能力水平往往较低。
一项比较普拉德 - 威利综合征缺失型和UPD型的大型研究结果与其他证据一致，表明15q11 - 13区域的父源印记基因构成了自闭症症状某些方面的遗传风险因素。因此，这些基因可能在自闭症病因中起作用。与另一项报告相反，缺失大小与认知和行为表型形式之间没有明确的关系。
