Identification and characterization of six β-crystallin gene mutations associated with congenital cataract in Chinese families.
Identification and characterization of six β-crystallin gene mutations associated with congenital cataract in Chinese families.
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中国家庭先天性白内障相关六种β-晶状体蛋白基因突变的鉴定和特征分析
DOI：
10.1002/mgg3.1617
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发表时间：
2021-03
影响因子：
2
通讯作者：
Yao K
中科院分区：
文献类型：
--
作者：
Yu Y;Qiao Y;Ye Y;Li J;Yao K
本研究旨在确定导致中国家庭先天性白内障的 β-晶状体蛋白 (CRYB) 基因的潜在遗传缺陷。记录了6个中国常染色体显性先天性白内障家系的详细家族史和临床资料。应用靶向外显子组测序来检测家庭潜在的遗传缺陷。生成的变体通过 PCR 和桑格测序进行确认。随后，通过几个计算预测程序进行生物信息分析，以评估突变对蛋白质结构和功能的影响。总共招募了来自 6 个无亲属关系的中国家庭的 53 名参与者（23 名受影响者和 30 名未受影响者）。白内障表型包括核性、全性、后极性、粉状、雪花状和小带性。通过靶向外显子组测序，揭示了4个β-晶状体蛋白基因的6个突变，其中包括5个错义突变CRYBB1 p.Q70P、CRYBB2 p.E23Q、CRYBB2 p.A49V、CRYBB2 R188C、CRYBA4 p.M14K和1个剪接突变CRYBB3 c.75+1 G>A。计算机结果预测除变体 CRYBB2-p.A49V 之外的所有四种错义变体均具有致病性，产生的结果为耐受性。 CRYBB3 c.75+1 G>A 剪接位点突变预计是有害的，会导致剪接位点断裂、过早终止密码子，并随后产生 113 个氨基酸的短肽，这可能会影响蛋白质特征。获得的结果扩大了β-晶状体蛋白基因的突变和表型谱，为先天性白内障的发病机制提供了线索。数据还表明，靶向外显子组测序对于为先天性白内障患者提供分子诊断信息很有价值。总共招募了来自 6 个无亲属关系的中国家庭的 53 名参与者（23 名受影响者和 30 名未受影响者）。白内障表型包括核性、全性、后极性、粉状、雪花状和小带性。通过靶向外显子组测序，揭示了4个β-晶状体蛋白基因的6个新突变，其中包括5个错义突变CRYBB1 p.Q70P、CRYBB2 p.E23Q、CRYBB2 p.A49V、CRYBB2 R188C、CRYBA4 p.M14K和1个剪接突变CRYBB3 c.75+1 G>A。
This study aims to identify the underlying genetic defects of β‐crystallin (CRYB) genes responsible for congenital cataracts in a group of Chinese families. Detailed family history and clinical data of six Chinese families with autosomal dominant congenital cataracts were recorded. Targeted exome sequencing was applied to detect the underlying genetic defects for the families. Generated variants were confirmed by PCR and sanger sequencing. Afterward, bioinformatic analysis through several computational predictive programs was performed to assess impacts of mutations on protein structure and function. A total of 53 participants (23 affected and 30 unaffected) from six unrelated Chinese families were recruited. Cataract phenotypes covered nuclear, total, posterior polar, pulverulent, snowflake‐like, and zonular. Through targeted exome sequencing, six mutations in four β‐crystallin genes were revealed which included five missense mutations CRYBB1 p.Q70P, CRYBB2 p.E23Q, CRYBB2 p.A49V, CRYBB2 R188C, CRYBA4 p.M14K and one splice mutation CRYBB3 c.75+1 G>A. In silico results predicted pathogenic for all four missense variants except variant CRYBB2‐p.A49V yielded results as tolerant. The CRYBB3 c.75+1 G>A splice site mutation was predicted to be deleterious by leading to a broken splice site, a premature stop codon, and subsequently resulting in a short peptide of 113 amino acids, which may affect protein features. The obtained results expanded mutational and phenotype spectrum of β‐crystallin genes and offer clues for pathogenesis of congenital cataracts. The data also demonstrated that targeted exome sequencing is valuable for providing molecular diagnostic information for congenital cataract patients. A total of 53 participants (23 affected and 30 unaffected) from six unrelated Chinese families were recruited. Cataract phenotypes covered nuclear, total, posterior polar, pulverulent, snowflake‐like, and zonular. Through targeted exome sequencing, six new mutations in four β‐crystallin genes were revealed which included five missense mutations CRYBB1 p.Q70P, CRYBB2 p.E23Q, CRYBB2 p.A49V, CRYBB2 R188C, CRYBA4 p.M14K, and one splice mutation CRYBB3 c.75+1 G>A.
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先天性白内障相关基因的靶向外显子组测序：拓宽27个中国汉族家系的突变谱和基因型-表型相关性
影响因子：
4.6
作者：
Zhai Y;Li J;Yu W;Zhu S;Yu Y;Wu M;Sun G;Gong X;Yao K
通讯作者：
Yao K
DOI：
10.1016/bs.pmbts.2015.04.006
发表时间：
2015
影响因子：
--
作者：
Hejtmancik JF;Shiels A
通讯作者：
Shiels A
DOI：
10.1159/000442495
发表时间：
2016-01-01
期刊：
PEDIATRIC CATARACT
影响因子：
--
作者：
Pichi, Francesco;Lembo, Andrea;Nucci, Paolo
通讯作者：
Nucci, Paolo
影响因子：
13.6
作者：
Moreau KL;King JA
通讯作者：
King JA
影响因子：
2
作者：
Astiazaran, Mirena C.;Garcia-Montano, Leopoldo A.;Zenteno, Juan C.
通讯作者：
Zenteno, Juan C.