Speech and language delay in a patient with WDR4 mutations
Speech and language delay in a patient with WDR4 mutations
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WDR4 突变患者的言语和语言发育迟缓
DOI：
10.1016/j.ejmg.2018.03.007
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发表时间：
2018-08-01
影响因子：
1.9
通讯作者：
Wang, Huijun
中科院分区：
文献类型：
--
作者：
Chen, Xiang;Gao, Yanyan;Wang, Huijun
原始侏儒症（PD）的主要特征是生长缺陷和异质性表型。已知一组基因与PD或PD相关综合征相关。WD重复结构域4 （WDR4）最近被报道与PD有关。我们在此报告一非近亲夫妇的六岁男童，患有运动及言语迟缓及智障。全外显子组测序（WES）鉴定出一个错义突变(NM_033661.4:c。491a > c；p.(Asp164Ala))和一个小的WDR4插入（NM_033661.4:c.940dupC; p.(Leu314Profs*16)）。Sanger测序证实的两个新突变分别来自父亲和母亲，根据隐性遗传模式。两种算法预测了位于功能区的Asp164Ala是有害的。引起移码突变的小插入导致蛋白质截短。在这项研究中，我们在一名6岁患者中发现了两个新的WDR4突变，扩大了WDR4相关PD的分子和表型谱。
Primordial dwarfism (PD) is mainly characterized by growth deficiency with heterogeneous phenotypes. A group of genes are known to be associated with PD or PD-related syndrome. WD repeat domain 4 (WDR4) is recently reported to be responsible for PD. Here we report a 6-year-old boy from a non-consanguineous couple with motor and speech delay as well as intellectual disability. Whole exome sequencing (WES) identified a missense mutation (NM_033661.4:c.491A > C; p.(Asp164Ala)) and a small insertion (NM_033661.4:c.940dupC; p. (Leu314Profs*16)) of WDR4 in this patient. Two novel mutations confirmed by Sanger sequencing are from father and mother respectively according to a recessive inheritance pattern. Asp164Ala located in functional region is predicted to be deleterious by two kinds of algorithm. The small insertion causing a frameshift mutation leads to truncated protein. In this study, we present two novel WDR4 mutations responsible for PD in a 6-year-old patient, expanding the molecular and phenotype spectrum of WDR4-related PD.