Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients.
Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients.
复制标题
中国患者 Wiedemann-Steiner 综合征的分子和表型谱描述
DOI：
10.1186/s13023-018-0909-0
复制
发表时间：
2018-10-11
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Li N;Wang Y;Yang Y;Wang P;Huang H;Xiong S;Sun L;Cheng M;Song C;Cheng X;Ding Y;Chang G;Chen Y;Xu Y;Yu T;Yao RE;Shen Y;Wang X;Wang J
Wiedemann-Steiner综合征（WDSTS）是一种罕见的以面部完形、神经发育迟缓、骨骼畸形和生长迟缓为特征的遗传性疾病，由KMT 2A基因变异引起。迄今为止，仅报告了2例中国WDSTS患者。在此，我们报告了14例无关的中国WDSTS患者的表型和KMT 2A基因变异，并调查了中国和法国队列之间的表型差异。 对每例患者进行下一代测序，并通过桑格测序验证KMT 2A基因中的变体。总结了16例中国WDSTS患者的表型，并与33例法国患者进行了比较。基因测序鉴定出14例患者的13种KMT 2A新变异，包括10种截短型、2种错义型和1种剪接型。在这13种变异中，11种是新的，2种以前曾报道过。其中一名患者的KMT 2A基因是嵌合体。中国WDSTS患者的变异谱和表型谱与其他种族患者无差异，但在几个临床特征的频率上存在差异。我们证明了KMT 2A基因的变异可以导致骨龄的提前和延迟。我们发现了6种新的表型，包括小头畸形、掌深折痕、外耳畸形、腕骨骨骺生长迟缓、血脂异常和舌下垂。此外，在KMT 2A的CXXC锌指结构域中具有错义变体的患者表现出更严重的神经表型。我们的研究包括最大的中国WDSTS患者队列，继续扩大WDSTS表型和变异谱。我们的研究结果支持了KMT 2A基因的CXXC锌指结构域是与更严重的神经表型相关的错义变体的热点的观点。本文的在线版本（10.1186/s13023-018-0909-0）包含补充材料，可供授权用户使用。
Wiedemann–Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts. Next generation sequencing was performed for each patient, and the variants in the KMT2A gene were validated by Sanger sequencing. The phenotypes of 16 Chinese WDSTS patients were summarized and compared to 33 French patients. Genetic sequencing identified 13 deleterious de novo KMT2A variants in 14 patients, including 10 truncating, 2 missenses and 1 splicing variants. Of the 13 variants, 11 are novel and two have been reported previously. One of the patients is mosaic in the KMT2A gene. The variation spectra and phenotypic profiles of the Chinese WDSTS patients showed no difference with patients of other ethnicities; however, differ in the frequencies of several clinical features. We demonstrated that variations in the KMT2A gene can lead to both advanced and delayed bone age. We identified 6 novel phenotypes, which include microcephaly, deep palmar crease, external ear deformity, carpal epiphyseal growth retardation, dyslipidemia, and glossoptosis. In addition, patients harbored missense variants in the CXXC zinc finger domain of KMT2A showed more severe neurophenotypes. Our study consists of the largest cohort of Chinese WDSTS patients that continues to expand the WDSTS phenotypic and variation spectrum. Our results support the notion that the CXXC zinc finger domain of KMT2A gene is a hotspot for missense variants associated with more severe neurophenotypes. The online version of this article (10.1186/s13023-018-0909-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
5.2
作者：
Sobreira, Nara;Brucato, Martha;Bjornsson, Hans T.
通讯作者：
Bjornsson, Hans T.
进一步描述截短 KMT2A 突变的表型：扩展的 Wiedemann-Steiner 综合征。
影响因子：
2
作者：
Sun, Yu;Hu, Guorui;Yu, Yongguo
通讯作者：
Yu, Yongguo
影响因子：
16
作者：
Milne, TA;Briggs, SD;Hess, JL
通讯作者：
Hess, JL
影响因子：
5.3
作者：
Bramswig, Nuria C.;Luedecke, Hermann-Josef;Wieczorek, Dagmar
通讯作者：
Wieczorek, Dagmar
仅先证者医学外显子组测序作为一种经济有效的一级基因诊断测试，适用于发展中国家没有事先进行分子测试和临床诊断的患者：中国经验
影响因子：
8.8
作者：
Hu, Xuyun;Li, Niu;Shen, Yiping
通讯作者：
Shen, Yiping