Cassidy S B, Gainey A J, Butler M G
Department of Pediatrics, University of Arizona College of Medicine, Tucson 84516.
Am J Hum Genet. 1989 Jun;44(6):806-10.
Prader-Willi syndrome (PWS) is a multiple-anomaly disorder in which 50%-70% of cases are associated with a de novo interstitial deletion [del 15(q11-13)] on prometaphase cytogenetic analysis, the remainder having apparently normal chromosomes. In most instances, the paternally derived chromosome has become deleted in the affected child, suggesting the possibility of a predisposing environmental factor. Strakowski and Butler found an increased incidence of paternal periconceptional employment in hydrocarbon-exposing occupations in this population. This observation may suggest a causal relationship to PWS. To determine whether this association may distinguish the cytogenetically different groups, we identified 81 patients with the disorder who were physically and cytogenetically examined in three centers, and we compared the frequency of possible periconceptional occupational hydrocarbon exposure between fathers of patients who demonstrate a 15q deletion and those who do not. There was no statistically significant difference between the cytogenetically different groups. In both groups, approximately half of the fathers had been employed in hydrocarbon-exposing jobs. These findings suggest lack of etiologic heterogeneity between the cytogenetically different groups for PWS and affirm the need to seek submicroscopic deletions through molecular genetic studies. These data also provide additional evidence that hydrocarbon exposure among fathers of children with PWS may be causally related to the disorder, and they also suggest the need for more accurate assessment of exposure via a large, controlled study.
普拉德-威利综合征（PWS）是一种多系统异常疾病，在中期细胞遗传学分析中，50%-70%的病例与新发的间质性缺失[del 15(q11-13)]相关，其余病例的染色体显然正常。在大多数情况下，患病儿童中父源染色体发生了缺失，这提示存在一种诱发环境因素的可能性。斯特拉科夫斯基和巴特勒发现，该人群中父亲在受孕前从事接触碳氢化合物职业的比例有所增加。这一观察结果可能提示与PWS存在因果关系。为了确定这种关联是否可以区分细胞遗传学上不同的组，我们在三个中心对81例患有该疾病的患者进行了体格检查和细胞遗传学检查，并比较了显示15q缺失的患者父亲与未显示15q缺失的患者父亲在受孕前可能接触职业性碳氢化合物的频率。细胞遗传学不同的组之间没有统计学上的显著差异。在两组中，大约一半的父亲曾从事接触碳氢化合物的工作。这些发现表明，PWS细胞遗传学不同的组之间缺乏病因异质性，并肯定了通过分子遗传学研究寻找亚显微缺失的必要性。这些数据还提供了额外的证据，表明PWS患儿父亲接触碳氢化合物可能与该疾病存在因果关系，并且它们还表明需要通过大规模的对照研究对接触情况进行更准确的评估。
