Kumar Manoj, Agarwal Tushar, Kaur Punit, Kumar Manoj, Khokhar Sudarshan, Dada Rima
Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Mol Vis. 2013 Nov 24;19:2436-50. eCollection 2013.
To determine the relative contributions of mutations in congenital cataract cases in an Indian population by systematic screening of genes associated with cataract.
We enrolled 100 congenital cataract cases presenting at the Dr. R. P. Centre for Ophthalmic Sciences, a tertiary research and referral hospital (AIIMS, New Delhi, India). Crystallin, alpha A (CRYAA), CRYAB, CRYGs, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, beaded filament structural protein 1 (BFSP1), gap function protein, alpha 3 (GJA3), GJA8, and heat shock transcription factor 4 gene genes were amplified. Protein structure differences analysis was performed using Discovery Studio (DS) 2.0.
The mean age of the patients was 17.45±16.51 months, and the age of onset was 1.618±0.7181 months. Sequencing analysis of 14 genes identified 18 nucleotide variations. Fourteen variations were found in the crystallin genes, one in Cx-46 (GJA3), and three in BFSP1.
Congenital cataract shows marked clinical and genetic heterogeneity. Five nucleotide variations (CRYBA4:p.Y67N, CRYBB1:p.D85N, CRYBB1:p.E75K, CRYBB1:p.E155K, and GJA3:p.M1V) were predicted to be pathogenic. Variants in other genes might also be involved in maintaining lens development, growth, and transparency. The study confirms that the crystallin beta cluster on chromosome 22, Cx-46, and BFSP1 plays a major role in maintaining lens transparency. This study also expands the mutation spectrum of the genes associated with congenital cataract.
通过对与白内障相关基因的系统筛查，确定印度人群先天性白内障病例中突变的相对贡献。
我们纳入了100例在印度新德里全印医学科学研究所（AIIMS）的三级研究和转诊医院——R.P.眼科科学中心就诊的先天性白内障病例。对αA晶状体蛋白（CRYAA）、CRYAB、CRYGs、CRYBA1、CRYBA4、CRYBB1、CRYBB2、CRYBB3、串珠丝状结构蛋白1（BFSP1）、缝隙连接蛋白α3（GJA3）、GJA8和热休克转录因子4基因进行扩增。使用Discovery Studio（DS）2.0进行蛋白质结构差异分析。
患者的平均年龄为17.45±16.51个月，发病年龄为1.618±0.7181个月。对14个基因的测序分析确定了18个核苷酸变异。在晶状体蛋白基因中发现了14个变异，在Cx - 46（GJA3）中发现1个，在BFSP1中发现3个。
先天性白内障表现出明显的临床和遗传异质性。五个核苷酸变异（CRYBA4:p.Y67N、CRYBB1:p.D85N、CRYBB1:p.E75K、CRYBB1:p.E155K和GJA3:p.M1V）被预测为致病性变异。其他基因的变异也可能参与维持晶状体的发育、生长和透明度。该研究证实，22号染色体上的晶状体蛋白β簇、Cx - 46和BFSP1在维持晶状体透明度方面起主要作用。本研究还扩展了与先天性白内障相关基因的突变谱。
