The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy.
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy.
复制标题
首例具有非典型 WHS 面部特征的中国父女中出现新变异的家族性 NSD2 病例以及生长激素治疗的 7.5 年随访
DOI：
10.1186/s12920-020-00831-9
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发表时间：
2020-12-04
影响因子：
2.7
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Hu X;Wu D;Li Y;Wei L;Li X;Qin M;Li H;Li M;Chen S;Gong C;Shen Y
背景
Wolf-Hirschhorn综合征是一种由4p16.3缺失引起的基因组疾病。Wolf-Hirschhorn综合征患者表现出特征性的面部畸形、生长迟缓、发育迟缓、智力残疾和癫痫发作障碍。最近，位于165 kb的Wolf-Hirschhorn综合征关键区域内的NSD 2基因被确定为负责大多数（如果不是全部）Wolf-Hirschhorn综合征表型的关键致病基因。到目前为止，已经在世界不同地区的患者中报告了8种NSD 2功能丧失变体，所有这些都是新发变体。
方法
在我们的研究中，我们对来自一个家庭的两名患者进行了全外显子组测序。我们还回顾了以往文献中更多的NSD 2突变病例。
结果
在一个中国家系中发现了一个新的NSD 2功能缺失变异体c.1577dupG（p.Asn527Lysfs*14），该家系的先证者及其父亲均患有智力残疾。在回顾了以往文献中更多的NSD 2突变病例后，我们发现没有一个病例具有可被识别为Wolf-Hirschhorn综合征的面部特征。此外，我们给我们的先证者生长激素，并随访了这个家庭7.5年。
结论
在这里，我们报道了第一个家族性NSD 2变异和生长激素治疗对患者的长期影响。提示NSD 2基因突变可能导致明显的智力残疾和身材矮小综合征。
Background
Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants.
Methods
In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature.
Results
A novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years.
Conclusions
Here we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome.
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