Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.8 P.727-734

Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing*

Author(s): Nan Hong¹,Yan-hua Chen¹,Chen Xie¹,Bai-sheng Xu¹,Hui Huang²,Xin Li²,Yue-qing Yang²,Ying-ping Huang²,Jian-lian Deng²,Ming Qi^2,3,4,Yang-shun Gu¹
Affiliation(s): 1. 1. Department of Ophthalmology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China more
Corresponding email(s): mingqi@zju.edu.cn
Key Words: Nance-Horan syndrome (NHS), Exome sequencing, X-linked disorder

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Nan Hong, Yan-hua Chen, Chen Xie, Bai-sheng Xu, Hui Huang, Xin Li, Yue-qing Yang, Ying-ping Huang, Jian-lian Deng, Ming Qi, Yang-shun Gu. Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing[J]. Journal of Zhejiang University Science B, 2014, 15(8): 727-734.

@article{title="Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing",
author="Nan Hong, Yan-hua Chen, Chen Xie, Bai-sheng Xu, Hui Huang, Xin Li, Yue-qing Yang, Ying-ping Huang, Jian-lian Deng, Ming Qi, Yang-shun Gu",
journal="Journal of Zhejiang University Science B",
volume="15",
number="8",
pages="727-734",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300321"
}

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%T Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing
%A Nan Hong
%A Yan-hua Chen
%A Chen Xie
%A Bai-sheng Xu
%A Hui Huang
%A Xin Li
%A Yue-qing Yang
%A Ying-ping Huang
%A Jian-lian Deng
%A Ming Qi
%A Yang-shun Gu
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 8
%P 727-734
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300321

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A1 - Nan Hong
A1 - Yan-hua Chen
A1 - Chen Xie
A1 - Bai-sheng Xu
A1 - Hui Huang
A1 - Xin Li
A1 - Yue-qing Yang
A1 - Ying-ping Huang
A1 - Jian-lian Deng
A1 - Ming Qi
A1 - Yang-shun Gu
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 8
SP - 727
EP - 734
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300321

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Objective: nance-Horan syndrome (NHS) is a rare x-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Methods: Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. Results: A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. Conclusions: We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.

全外显子组测序发现一个中国Nance-Horan综合征家系NHS基因的新突变

研究目的：通过对一个中国Nance-Horan综合征家系的临床表型及基因突变分析，揭示本家系的致病遗传机制。
研究方法：对该Nance-Horan综合征家系的一个男性患者进行全外显子组测序，结合此家系临床表型及遗传方式分析，选定X染色体上NHS基因上的一个无义突变c.322G>T（E108X）为可疑致病突变。通过聚合酶链式反应（PCR）和Sanger测序，对该家系内其他成员进行NHS基因突变分析，同时对50名健康对照者的NHS基因的突变检测结果进行对比。另外，将该突变的位点第108位氨基酸残基进行多物种NHS蛋白内序列比对。最后，对该家系成员眼部及全身的临床特点进行全面检查和分析。
重要结论：全外显子组测序结合Sanger测序发现NHS基因第一个外显子上的c.322G>T（E108X）突变为引起该家系临床病变的突变位点；多物种NHS蛋白内序列比对发现该突变位点第108位氨基酸残基位于高度保守区；临床表型分析发现该家系内存在表型异质性。此家系为国内首次报道的无义突变引起的Nance-Horan综合征家系。
Nance-Horan综合征；NHS；外显子测序；X-连锁