Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.
Genes Genomics. 2024 Aug;46(8):917-925. doi: 10.1007/s13258-024-01525-7. Epub 2024 Jun 13.
Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children's visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients.
This investigation aimed to discover causative mutations in four separate Chinese family lineages.
The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein.
The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations.
Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients.
先天性白内障是由环境影响和遗传易感性等多种因素共同作用引起的，它会对全球儿童的视觉健康造成严重影响。先天性白内障的发病率为每 10000 例新生儿中有 0.63 至 9.74 例，每 10000 例儿童中有 7.4 例，亚洲的发病率最高。该疾病的症状包括晶状体混浊和视力障碍。及时发现该疾病对于儿科患者的治疗和预后至关重要。
本研究旨在发现四个中国家族系中导致疾病的突变。
详细记录了四个中国常染色体显性遗传性先天性白内障家系的临床资料和家族史。对全外显子组测序结果进行分析，以确定家系中存在的遗传异常。随后通过 PCR 和 Sanger 测序对鉴定出的突变进行验证。利用多种计算预测程序评估这些突变对蛋白质结构和功能的影响。
测序结果显示了四个潜在的致病突变：CRYBB2 家族 1 中的 c.436G > A（p.V146M），GJA3 中的 c.26G > T（p.R9I），GJA8 中的 c.227G > A（p.R76H），FTL 中的 c.-168G > T。其中，GJA3 家系中的致病突变是新发现的，FTL 家系是一种罕见的白内障综合征。这些家系中的突变与受影响个体完全共分离，而在未受影响的家系成员或 100 名对照者中未发现这些突变。几个生物信息学预测工具也支持这些突变的可能致病性。
我们的研究结果扩展了与先天性白内障相关的基因突变和表型谱，并为先天性白内障的发病机制提供了线索。这些数据还证明了 NGS 技术对于先天性白内障患者分子诊断的重要性。
