Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Am J Med Genet A. 2010 Jan;152A(1):102-10. doi: 10.1002/ajmg.a.33160.
Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of approximately 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36.
1p36 重排是染色体隐匿性不平衡诊断检测中最常发现的异常，包括大小不等的简单末端缺失、衍生染色体、中间缺失和复杂重排。这些重排导致了单体 1p36 综合征特有的畸形和神经发育障碍模式。到目前为止，该区域内还没有一个单一基因被确定为表型的任何组成部分的致病原因。也不知道这些重排是否通过杂合不足机制或位置效应来传递表型。我们使用多重连接依赖性探针扩增技术，对 154 名贪食和超重/肥胖、PWS 阴性个体进行了 1p36 缺失筛查，并对 83 名最初因各种其他疾病而接受检查的患者进行了另一项筛查。该策略能够鉴定和描绘 9 名具有广泛临床表现的个体的重排。我们的工作加强了单体 1p36 与肥胖和贪食的关联，并进一步表明，除了大小约为 2-3Mb 的亚微缺失外，这些特征可能与该疾病的非典型表现相关。使用单体 1p36 综合征特异性试剂盒和端粒下试剂盒的多重连接探针扩增是识别和描绘 1p36 重排的有效方法。
