De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
复制标题
NSD2基因的从头截短变异导致非典型沃尔夫-赫希霍恩综合征表型
DOI：
10.1186/s12881-019-0863-2
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发表时间：
2019-08-05
影响因子：
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通讯作者：
Yao, Ruen
中科院分区：
文献类型：
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作者：
Jiang, Yanrui;Sun, Huizhen;Yao, Ruen
背景：沃尔夫-赫希霍恩综合征（WHS）是一种由部分4p缺失引起的连续基因综合征，个体患者的大小差异很大。WHS的核心表型由生长迟缓、典型面部特征、智力残疾和癫痫发作的关联来定义。WHS临界区域（WHSCR）已经缩小，nsd2就在这个200kb的区域内。只有4例nsd2变异患者被详细记录了表型特征。在此，我们报告一个12岁男孩发育迟缓的病例。他有畸形的面部特征，包括宽间距的眼睛，突出的鼻梁持续前额，牙齿异常和小颌。他也有轻微的双手倾斜。通过全外显子组测序，我们鉴定出致病突变insd2 [c]。4029_4030insAA, p.Glu1344Lysfs*49]从外周血DNA中分离得到。桑格对这一变异的确认表明，它是家族中一个从头开始的截断变异。结论：我们报道了一名男婴新生截断型innsd2，与4p16.3缺失相关的WHS相比，其临床特征不典型。我们的发现进一步支持了截断变异insd2的发病机制，并描绘了由这些变异引起的可能的症状谱。
BackgroundWolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down andNSD2falls within this 200 kb region. Only four patients withNSD2variants have been documented with phenotypic features in detail.Case presentationHerein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation inNSD2[c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family.ConclusionHere, we reported a boy with de novo truncating variant inNSD2with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants inNSD2and delineated the possible symptom spectrum caused by these variants.