De novo nonsense mutation in WHSC1 (NSD2) in patient with intellectual disability and dysmorphic features
De novo nonsense mutation in WHSC1 (NSD2) in patient with intellectual disability and dysmorphic features
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DOI：
10.1038/s10038-018-0464-5
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发表时间：
2018-07-01
影响因子：
3.5
通讯作者：
Korostelev, Sergey A.
中科院分区：
文献类型：
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作者：
Lozier, Ekaterina R.;Konovalov, Fedor A.;Korostelev, Sergey A.
智力残疾是由染色体畸变以及单核苷酸变异（SNV）和小插入/缺失（indels）引起的最常见的发育障碍。在这里，我们报告了一个新的，可能是致病性突变的WHSC 1基因的患者的情况下，表型重叠的特点沃尔夫-赫希霍恩综合征。早期在Wolf-Hirschhorn综合征患者中描述了涉及WHSC 1（Wolf-Hirschhorn综合征候选基因1）的缺失。然而，据我们所知，WHSC 1的单点突变与任何智力缺陷综合征还没有报道。采用全外显子测序技术，我们发现一位综合征型智力残疾患者WHSC 1基因存在一个无义突变（c.3412C>T，p.Arg1138Ter，NM_001042424.2）。这一发现对于WHSC 1在智力残疾综合征，特别是Wolf-Hirschhorn综合征中可能的致病作用具有挑战性。从临床的角度来看，我们的发现表明，下一代测序沿着染色体微阵列分析（CMA）可能是有用的智力残疾和畸形特征的患者的基因检测。
Intellectual disability is the most common developmental disorder caused by chromosomal aberrations as well as single-nucleotide variants (SNVs) and small insertions/deletions (indels). Here we report identification of a novel, probably pathogenic mutation in the WHSC1 gene in a patient case with phenotype overlapping the features of Wolf-Hirschhorn syndrome. Deletions involving WHSC1 (Wolf-Hirschhorn syndrome candidate 1 gene) were described earlier in patients with Wolf-Hirschhorn syndrome. However, to our knowledge, single-point mutations in WHSC1 associated with any intellectual deficiency syndromes have not been reported. Using whole exome sequencing, we found a de novo nonsense mutation in WHSC1 (c.3412C>T, p.Arg1138Ter, NM_001042424.2) in patient with syndromic intellectual disability. This finding is challenging regarding a possible causative role of WHSC1 in intellectual disability syndromes, specifically Wolf-Hirschhorn syndrome. From the clinical standpoint, our finding suggests that next-generation sequencing along with chromosome microarray analysis (CMA) might be useful in genetic testing for patients with intellectual disability and dysmorphic features.