Extending the Phenotype of Monosomy 1p36 Syndrome and Mapping of a Critical Region for Obesity and Hyperphagia
Extending the Phenotype of Monosomy 1p36 Syndrome and Mapping of a Critical Region for Obesity and Hyperphagia
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DOI：
10.1002/ajmg.a.33160
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
Koiffmann, Celia P.
中科院分区：
文献类型：
--
作者：
D'Angelo, Carla S.;Kohl, Ilana;Koiffmann, Celia P.
1p36的重排是染色体隐性失衡诊断检测中最常检测到的异常，包括大小不一的简单末端缺失、衍生染色体缺失、间质缺失和复杂重排。这些重排导致了1p36单体综合征特有的畸形和神经发育障碍。到目前为止，在这一区域内还没有任何单个基因被确定为导致表型的任何组成部分。也不知道重排是通过单倍不足机制还是通过位置效应传递表型。我们使用多重连接依赖探针扩增来筛选154名贪食和超重/肥胖、PWS阴性个体以及83名最初被派去调查各种其他疾病的患者的1p36缺失。该策略允许在9个具有广泛临床表现的受试者中识别和描述重排。我们的工作强化了单体1p36与肥胖和贪食的关联，并进一步表明，除了类似于2-3 Mb大小的亚显微镜缺失外，这些特征可能与该疾病的非经典表现有关。使用单体1p36综合征特异性试剂盒与亚端粒试剂盒相结合的多重连接探针扩增是识别和描述1p36重排的有效方法。(C) 2009 Wiley-Liss, Inc。
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 similar to 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. (C) 2009 Wiley-Liss, Inc.