Wang Kai Jie, Wang Bin Bin, Zhang Fengju, Zhao Yanyan, Ma Xu, Zhu Si Quan
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
Arch Ophthalmol. 2011 Mar;129(3):337-43. doi: 10.1001/archophthalmol.2011.11.
To investigate the molecular genetic background in families with nuclear congenital cataract.
Family history and clinical data were recorded. Ten candidate genes were screened for causative mutations. Direct sequencing was performed to analyze the cosegregation of the genotype with the disease phenotype. Effects of amino acid changes on the structure and function of protein were predicted by bioinformatics analysis.
Analyses of 20 Chinese families with hereditary nuclear congenital cataract revealed 3 novel mutations. Two of these mutations (V146M and I21N) affected βB2-crystallin (CRYBB2). One mutation (R233H) was detected in βB1-crystallin (CRYBB1). These mutations cosegregated with all affected individuals and were not observed in unaffected family members or the 150 healthy unrelated individuals.
The CRYBB2 gene was shown to be another causative gene associated with congenital cataract and microcornea. Three novel mutations in β-crystallin genes (CRYB) were detected in Chinese families with nuclear autosomal dominant congenital cataracts, which underscores the genetic heterogeneity of this condition.
Studying the genetics of nuclear cataracts is helpful for better understanding the pathophysiologic mechanisms that underlie this phenotype and for better disease management. This study helps expand the genotype of nuclear cataract and microcornea.
研究核性先天性白内障患者家系的分子遗传背景。
记录家族史和临床资料。筛选10个候选基因以寻找致病突变。采用直接测序法分析基因型与疾病表型的共分离情况。通过生物信息学分析预测氨基酸变化对蛋白质结构和功能的影响。
对20个遗传性核性先天性白内障中国家系的分析发现了3个新突变。其中两个突变（V146M和I21N）影响βB2-晶体蛋白（CRYBB2）。在βB1-晶体蛋白（CRYBB1）中检测到一个突变（R233H）。这些突变与所有患病个体共分离，在未患病家庭成员或150名健康无关个体中未观察到。
CRYBB2基因被证明是与先天性白内障和小角膜相关的另一个致病基因。在中国核性常染色体显性先天性白内障家系中检测到β-晶体蛋白基因（CRYB）的3个新突变，这突出了该疾病的遗传异质性。
研究核性白内障的遗传学有助于更好地理解该表型的病理生理机制并改善疾病管理。本研究有助于扩展核性白内障和小角膜的基因型。
