Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity
Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity
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DOI：
10.1038/gim.2014.124
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发表时间：
2015-06-01
影响因子：
8.8
通讯作者：
Menten, Bjoern
中科院分区：
文献类型：
--
作者：
De Rocker, Nina;Vergult, Sarah;Menten, Bjoern
目的：染色体2p25.3亚显微缺失与智力障碍和/或中心性肥胖有关。虽然Myt1l被认为是导致智能障碍的关键基因，但到目前为止还没有明确的数据证实这一假设。方法：在这项研究中，我们评估了22例2p25.3异常的患者(15名散发性患者和两个家系)，以进一步完善临床表型，并描述Myt1l在智能障碍和肥胖中的作用。结果：除2例Myt1基因点突变外，所有散发性患者均存在Myt1基因的完全缺失、基因内缺失或复制。家族性病例包括父亲和他的三个孩子的6-Mb缺失和父亲和他的两个孩子的5‘Myt1重叠重复。斑马鱼胚胎中的表达分析表明Myt1在发育中的大脑中特异表达。结论：我们的数据有力地支持了Myt1是所观察到的综合征性智能障碍的原因基因的假设。此外，由于17名患者存在肥胖/超重，Myt1基因单倍性不足可能容易导致儿童发病的体重问题。
Purpose: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis.Methods: In this study we evaluated a cohort of 22 patients (15 sporadic patients and two families) with a 2p25.3 aberration to further refine the clinical phenotype and to delineate the role of MYT1L in intellectual disability and obesity. In addition, myt1l spatiotemporal expression in zebrafish embryos was analyzed by quantitative polymerase chain reaction and whole-mount in situ hybridization.Results: Complete MYT1L deletion, intragenic deletion, or duplication was observed in all sporadic patients, in addition to two patients with a de novo point mutation in MYT1L. The familial cases comprise a 6-Mb deletion in a father and his three children and a 5' MYT1L overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific myt1l expression in the developing brain.Conclusion: Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.