A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability
A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability
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DOI：
10.1002/ajmg.a.40370
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发表时间：
2018-09-01
影响因子：
2
通讯作者：
Makitie, Outi
中科院分区：
文献类型：
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作者：
Loid, Petra;Makitie, Riikka;Makitie, Outi
严重早发性肥胖的遗传背景尚不完全清楚。2p25.3缺失与早发性肥胖和可变智力残疾有关。该基因座的髓鞘转录因子-1样（MYT1L）基因被认为是肥胖的候选基因。我们报告了一名13岁男孩在1岁时就表现出超重（身体质量指数[BMI] Z-score +2.3）和2岁时肥胖（BMI Z-score +3.8）。患者出现吞咽过多，神经、认知和运动发育迟缓。他还患有语言迟缓、斜视、多动症和智力残疾。脑MRI正常。父母和妹妹的身体质量指数正常。全基因组测序在索引患者中发现了一种新的新移码缺失，该移码缺失导致MYT1L的翻译过早终止：c.2215_2224delACGCGCTGCC, p.（Thr739Alafs*7）。通过Sanger测序证实了移码变异。我们的发现支持MYT1L突变与早发综合征性肥胖的关联。儿童肥胖的新单基因形式的识别将提供有关遗传和生物学途径的见解。
The genetic background of severe early-onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early-onset obesity and variable intellectual disability. Myelin-transcriptor-factor-1-like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13-year-old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z-score +2.3) and obesity at 2 years of age (BMI Z-score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development. He also had speech delay, strabismus, hyperactivity and intellectual disability. Brain MRI was normal. The parents and sister had normal BMI. Whole-genome sequencing identified in the index patient a novel de novo frameshift deletion that introduces a premature termination of translation NM_015025.2(MYT1L): c.2215_2224delACGCGCTGCC, p.(Thr739Alafs*7) in MYT1L. The frameshift variant was confirmed by Sanger sequencing. Our finding supports the association of MYT1L mutations with early-onset syndromic obesity. The identification of novel monogenic forms of childhood-onset obesity will provide insights to the involved genetic and biologic pathways.