Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Tamil Nadu 600 113, India.
Institute of Developmental Genetics, Helmholtz Zentrum Munchen, D-85764 Munich, Germany.
Int J Mol Sci. 2020 Dec 16;21(24):9569. doi: 10.3390/ijms21249569.
Congenital cataracts are the prime cause for irreversible blindness in children. The global incidence of congenital cataract is 2.2-13.6 per 10,000 births, with the highest prevalence in Asia. Nearly half of the congenital cataracts are of familial nature, with a predominant autosomal dominant pattern of inheritance. Over 38 of the 45 mapped loci for isolated congenital or infantile cataracts have been associated with a mutation in a specific gene. The clinical and genetic heterogeneity of congenital cataracts makes the molecular diagnosis a bit of a complicated task. Hence, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 11 pedigrees affected with familial congenital cataracts. Analysis of the WES data for known cataract genes identified causative mutations in six pedigrees (55%) in (two variants), and an additional likely causative mutation in a novel gene , which represents the first dominant mutation in this gene. This study identifies a novel cataract gene not yet linked to human disease. NCOA6 is a transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator function.
先天性白内障是儿童不可逆转失明的主要原因。全球先天性白内障的发病率为每 10000 例出生中有 2.2-13.6 例，亚洲的发病率最高。近一半的先天性白内障具有家族性，以常染色体显性遗传为主。在 45 个已定位的孤立性先天性或婴儿期白内障基因座中，有超过 38 个与特定基因的突变有关。先天性白内障的临床和遗传异质性使得分子诊断变得有些复杂。因此，我们利用外显子组测序（WES）同时筛选所有已知的白内障基因，并在 11 个受家族性先天性白内障影响的家系的先证者中检查新的候选致病突变因素。对已知白内障基因的 WES 数据分析在六个家系（55%）中鉴定出了致病突变（两个变体），在一个新基因 中鉴定出了另一个可能的致病突变，这是该基因中的第一个显性突变。这项研究确定了一个尚未与人类疾病相关的新的白内障基因。NCOA6 是一种转录共激活因子，与核激素受体相互作用，增强其转录激活功能。
