Mutation screening of crystallin genes in Chinese families with congenital cataracts
Mutation screening of crystallin genes in Chinese families with congenital cataracts
复制标题
中国先天性白内障家系晶状体蛋白基因突变筛查
作者：
Jianfu Zhuang;Zongfu Cao;Yihua Zhu;Lijua Liu;Yi Tong;Xiaole Chen;Yaduan Wang;Cailing Lu;Xu Ma;Juhua Yang
目的检测中国先天性白内障家系晶状体蛋白基因突变。方法收集42个无血缘关系的非综合征性先天性白内障家系。用桑格测序法对晶状体蛋白基因的外显子及邻近内含子区进行分析，这些基因包括晶状体蛋白AA、晶状体蛋白AB、晶状体蛋白BA 1、晶状体蛋白BA 4、晶状体蛋白BB 1、晶状体蛋白BB 2、晶状体蛋白BB 3、晶状体蛋白GC、晶状体蛋白GD和晶状体蛋白GS。在112个种族匹配的对照中进一步评估了新的变体。为了证实新的突变，短串联重复序列（STR）单倍型构建，以检查与先天性白内障的共分离。使用生物信息学工具评估了新突变的致病潜力，包括Sorting Intolerant From Tolerant v5.1.1（SIFT），Polymorphism Phenotyping v2（PolyPhen-2）和Human Splicing tumor。根据美国医学遗传学学会（ACMG）的指南和InterVar软件评估所有突变的致病性。结果在10个无亲缘关系的家系中发现7个晶体蛋白基因突变与先天性核性白内障相关。在4个无血缘关系的先天性白内障家系中发现了4个晶状体蛋白基因的新突变，包括c.35G>T（p.R12L）、c.463C>A（p.Q155K）、c.10-1G>A（c.116Sfsx29）和c.346delT（p.F116Sfsx29）。这些突变与每个家庭中所有受影响的个体共分离，在未受影响的家庭成员或112个无关的对照中未观察到。根据ACMG标准，使用InterVar软件，将所有四种新突变分类为疾病“可能致病”，除了IVS 1 c.10-1G>A在IGGC中为“致病”。晶状体蛋白基因突变与33.33%的先天性白内障家系有关。结论本研究在中国先天性白内障家系中发现了4个晶状体蛋白基因的新突变。该结果扩大了晶体蛋白基因的突变谱，这可能有助于精准医学时代先天性白内障的分子诊断。
Purpose To identify mutations in crystallin genes in Chinese families with congenital cataracts. Methods Forty-two unrelated families with non-syndromic congenital cataracts were enrolled in this study. The coding exons and adjacent intronic regions of crystallin genes, including CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD and CRYGS, were analyzed with Sanger sequencing. Novel variants were further evaluated in 112 ethnically matched controls. To confirm the novel mutations, short tandem repeat (STR) haplotypes were constructed to check the cosegregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools, including Sorting Intolerant From Tolerant v5.1.1 (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Human Splicing Finder. The pathogenicity of all the mutations was evaluated according to the guidelines of the American College of Medical Genetics (ACMG) and InterVar software. Results Seven previously reported mutations in crystallin genes identified in ten unrelated families were associated with the congenital nuclear cataracts. Four novel mutations in crystallin genes, including c.35G>T (p.R12L) in CRYAA, c.463C>A (p.Q155K) in CRYBB2, IVS1 c.10–1G>A in CRYGC, and c.346delT (p.F116Sfsx29) in CRYGD, were identified in four unrelated families with congenital cataracts. These mutations cosegregated with all affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. All four novel mutations were categorized as disease “likely pathogenic” except IVS1 c.10–1G>A in CRYGC “pathogenic” using InterVar software in accordance with the ACMG standard. Mutations in crystallin genes were responsible for 33.33% of the Chinese families with congenital cataracts in this cohort. Conclusions In this study, we identified four novel mutations in crystallin genes in Chinese families with congenital cataracts. The results expand the mutational spectrum of crystallin genes, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.
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影响因子：
3.4
作者：
Augusteyn, Robert C.
通讯作者：
Augusteyn, Robert C.
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：
10.1038/gim.2014.148
发表时间：
2015-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
HSF4新突变导致中国家庭先天性白内障
影响因子：
--
作者：
Cao Z;Zhu Y;Liu L;Wu S;Liu B;Zhuang J;Tong Y;Chen X;Xie Y;Nie K;Lu C;Ma X;Yang J
通讯作者：
Yang J
影响因子：
4.4
作者：
J. Bateman;J. Bateman;D. Geyer;P. Flodman;M. Johannes;J. Sikela;N. Walter;A. T. Moreira;
通讯作者：
J. Bateman;J. Bateman;D. Geyer;P. Flodman;M. Johannes;J. Sikela;N. Walter;A. T. Moreira;