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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.5 P.421-429

http://doi.org/10.1631/jzus.B1600156


Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis


Author(s):  Yun Li, Qing Pan, Yang-shun Gu

Affiliation(s):  Department of Ophthalmology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   guyangshun_1@hotmail.com

Key Words:  Leber congenital amaurosis, Phenotype-genotype correlation, RDH12, Compound heterozygosity


Yun Li, Qing Pan, Yang-shun Gu. Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis[J]. Journal of Zhejiang University Science B, 2017, 18(5): 421-429.

@article{title="Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis",
author="Yun Li, Qing Pan, Yang-shun Gu",
journal="Journal of Zhejiang University Science B",
volume="18",
number="5",
pages="421-429",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600156"
}

%0 Journal Article
%T Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis
%A Yun Li
%A Qing Pan
%A Yang-shun Gu
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 5
%P 421-429
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600156

TY - JOUR
T1 - Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis
A1 - Yun Li
A1 - Qing Pan
A1 - Yang-shun Gu
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 5
SP - 421
EP - 429
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600156


Abstract: 
Background: leber congenital amaurosis (LCA) is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations. Methods: A Chinese family with six members including two individuals affected with LCA was studied. All patients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes. Results: By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 (RDH12) gene: a c.164C>A transversion predicting a p.T55K substitution, and a c.535C>G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls. Besides, the RDH12 variants were confirmed by targeted next-generation sequencing. Conclusions: The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.

临床表型-基因型关联发现Leber先天性黑矇(LCA)家系新的RDH12基因复合杂合突变

目的:临床表型-基因型关联分析筛查Leber先天性黑矇(LCA)家系候选基因,确定其分子遗传病因。
创新点:成功应用临床表型-基因型关联分析鉴定LCA家系致病基因,并发现新的RDH12基因复合杂合突变。
方法:收集一个中国常染色体隐性遗传三代LCA家系,详细分析该家系眼部表型特征(图1和表1),经临床表型-基因型关联分析确定RDH12为候选基因。Sanger测序发现新的RDH12基因复合杂合突变(图2),目标序列捕获高通量测序技术排除其他已知LCA相关基因(表2)。该家系成员基因型显示完整的共分离(图3),同时在600例普通人群中未发现该突变。
结论:RDH12基因复合杂合突变可能为该LCA家系的致病基因,临床表型-基因型关联分析在LCA分子遗传学诊断中有重要价值。

关键词:Leber先天性黑矇;临床表型-基因型关联;RDH12;复合杂合突变

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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