Shimada Shino, Maegaki Yoshihiro, Osawa Makiko, Yamamoto Toshiyuki
Am J Med Genet A. 2014 Feb;164A(2):415-20. doi: 10.1002/ajmg.a.36304.
We identified mosaic 1p36 deletions in two patients with developmental delay, distinctive features, and obesity, who can walk alone and communicate with others. Thus, their neurological defects are milder than those in typical patients with 1p36 deletion syndrome because most patients with 1p36 deletion cannot acquire expressive language. Chromosomal microarray testing revealed 3.0 and 4.5 Mb aberrations in the subtelomeric region of the short arm of chromosome 1. Mean signal ratios of the identified aberrations were -0.4 and -0.5, indicating mosaicism, which was confirmed by fluorescence in situ hybridization analysis with a mosaic ratio of 70% and 77%, respectively. Previous studies demonstrated that deletion of the distal 2-3 Mb region would be responsible for hyperphagia and obesity seen in patients. On the other hand, the severity of the neurological defect often correlates with the size of the terminal deletion of 1p36, and patients with larger deletions of 1p36 would usually show severely impaired developmental milestones and be immobile and aphasic. In such cases, hyperphagia and obesity could be clinically masked. In this study, two patients with mosaic deletions of 1p36 showed obesity as a consequence of hyperphagia. This study suggests that patients with 1p36 deletion would be at risk for hyperphagia and obesity when they have both risk factors, that is, (1) deletions including the 2-3 Mb critical region and (2) milder phenotypes that allow them to reach food on their own and to overeat.
我们在两名发育迟缓、具有独特特征且肥胖的患者中发现了1p36染色体的镶嵌性缺失，这两名患者能够独立行走并与他人交流。因此，他们的神经缺陷比典型的1p36缺失综合征患者要轻，因为大多数1p36缺失患者无法获得表达性语言能力。染色体微阵列检测显示1号染色体短臂亚端粒区域存在3.0和4.5 Mb的畸变。所识别畸变的平均信号比分别为-0.4和-0.5，表明存在镶嵌现象，荧光原位杂交分析证实了这一点，镶嵌比例分别为70%和77%。先前的研究表明，远端2 - 3 Mb区域的缺失会导致患者出现贪食和肥胖。另一方面，神经缺陷的严重程度通常与1p36末端缺失的大小相关，1p36缺失较大的患者通常会表现出发育里程碑严重受损、无法活动和失语。在这种情况下，贪食和肥胖在临床上可能会被掩盖。在本研究中，两名1p36镶嵌性缺失的患者因贪食而出现肥胖。本研究表明，当1p36缺失患者同时具备以下两个危险因素时，即(1)包括2 - 3 Mb关键区域的缺失和(2)较轻的表型，使其能够自行获取食物并过量进食，他们就有患贪食和肥胖的风险。
