[Bainbridge-Ropers syndrome with ASXL3 gene variation in a child and literature review].
[Bainbridge-Ropers syndrome with ASXL3 gene variation in a child and literature review].
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DOI：
10.3760/cma.j.issn.0578-1310.2018.02.013
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发表时间：
2018-02-02
期刊：
影响因子：
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通讯作者：
Yang, X H
中科院分区：
文献类型：
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作者：
Zhang, R;He, X H;Yang, X H
目的：探讨1例ASXL3基因变异引起的儿童Bainbridge-Ropers综合征的临床表现和遗传特征，并复习文献。方法：收集并分析宝安市妇幼保健院2016年11月确诊的1例Bainbridge-Ropers综合征患儿的临床资料和基因特征。以“ASXL3”和“Bainbridge-Ropers”为关键词，检索中国国家知识基础设施、旺方数据知识服务平台、PubMed和人类基因突变数据库，截至2017年6月。结果：1例2岁(9/12)女童表现为精神运动迟缓、进食困难、低眼压和特殊的头面部表型。严重生长迟缓(身高84 cm，体重8.0 kg，均小于同龄儿童第3百分位数)，头围46 cm(=第3百分位数)，实验室检查及神经影像检查无明显异常。通过全外显子测序鉴定出ASXL3基因中一个新的杂合无义变异：C.3349C>；T(p.R1117*)，并根据ACMG的序列变异解释标准和指南将该新变异归类为病理性变异。根据文献检索，未见中国人ASXL3变异病例的报道。本文报告了28例ASXL3变异的病例，包括这位女孩，并有详细的临床资料。共发现31个ASXL3基因变异，其中错义变异1个，功能丧失变异30个，均为从头变异。结论：Bainbridge-Ropers综合征的临床特征为严重的精神运动发育迟缓、进食困难、低眼压和特殊的面部特征。ASXL3基因杂合性无义变异是患者的病因。ASXL3基因的致病变异均为从头变异和功能丧失变异。
Objective: To investigate the clinical manifestations and genetic features of a child with Bainbridge-Ropers syndrome caused by ASXL3 gene variation and review the literature. Methods: Clinical data and genetic features were collected and analyzed from a child with Bainbridge-Ropers syndrome who was diagnosed in Bao'an Maternity and Child Health Hospital in November 2016. "ASXL3" and "Bainbridge-Ropers" were used as key words to search at China National Knowledge Infrastructure, Wangfang Data Knowledge Service Platform, PubMed and Human Gene Mutation Database up to June 2017. Results: A 2(9/12) years old girl was presented with psychomotor retardation, feeding difficulty, hypotonia and specific craniofacial phenotype. She showed severe growth retardation (height: 84 cm, body weight: 8.0 kg (both were less than 3(rd) percentile rank of the children at the same age) and head circumference: 46 cm(=3rd percentile rank)), without obvious abnormalities in laboratory tests and neuroimaging tests. A de novo heterozygous nonsense variation: c.3349C>T(p.R1117*) in ASXL3 gene was identified by the whole exome sequencing, and the novel variation was classified into pathologic variant based on Standards and guidelines for the interpretation of sequence variants from ACMG. According to literature retrieval, no Chinese cases with ASXL3 variation had been reported. Totally 28 cases including the present girl harboring ASXL3 variations with detailed clinical information were reported. Thirty-one variations in ASXL3 gene were involved, including 1 missense variation and 30 loss of function variations, which were all de novo variations. Conclusions: The clinical features of Bainbridge-Ropers syndrome include severe psychomotor retardation, feeding difficulties, hypotonia and specific facial features. The heterozygous nonsense variation in ASXL3 gene is the cause of the patient. All the pathogenic variations in ASXL3 gene are de novo and loss of function variations.