Abstract：
BACKGROUND: 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.
OBJECTIVE: This investigation aimed to discover causative mutations in four separate Chinese family lineages.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: This investigation aimed to discover causative mutations in four separate Chinese family lineages.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：先天性白内障，这可能是由于环境影响和遗传易感性等因素的组合而产生的，显著影响全球儿童的视觉健康。先天性白内障的发生率从0。每10,000名新生儿63至9.74名。每10,000名儿童有7.4个实例，在亚洲的发病率最高。该疾病的症状包括晶状体混浊和视力障碍。及时识别病情对儿科患者的管理和展望起着至关重要的作用。
目的：本研究旨在发现四个独立的中国家族谱系中的致病突变。
方法：仔细记录了四个常染色体显性遗传先天性白内障中国家庭的详细临床资料和家族史。全外显子组测序的检查用于鉴定家族性病例中存在的遗传异常。随后使用PCR和Sanger测序对鉴定的突变进行验证。在此之后,各种计算预测程序被用来评估突变如何影响蛋白质的结构和功能。
结果：测序结果揭示了四个潜在的致病突变：c.436G>A（p。CRYBB2家族1的V146M），c.26G>T（p。家族2中GJA3的R9I），c.227G>A（p。家族3中GJA8的R76H），c.-168G>家族4中FTL的T。其中,GJA3家族的致病突变是新的，家庭FTL是一种罕见的白内障综合征。这些家族性突变显示与受影响的个体完全共分离，不存在未受影响的家庭成员或100个对照。几种生物信息学预测工具也支持这些突变的可能致病性。
结论：我们的发现扩展了先天性白内障相关基因的突变和表型谱，为先天性白内障的发病机制提供了线索。这些数据也证明了NGS技术对于先天性白内障患者的分子诊断的重要性。
目的：本研究旨在发现四个独立的中国家族谱系中的致病突变。
方法：仔细记录了四个常染色体显性遗传先天性白内障中国家庭的详细临床资料和家族史。全外显子组测序的检查用于鉴定家族性病例中存在的遗传异常。随后使用PCR和Sanger测序对鉴定的突变进行验证。在此之后,各种计算预测程序被用来评估突变如何影响蛋白质的结构和功能。
结果：测序结果揭示了四个潜在的致病突变：c.436G>A（p。CRYBB2家族1的V146M），c.26G>T（p。家族2中GJA3的R9I），c.227G>A（p。家族3中GJA8的R76H），c.-168G>家族4中FTL的T。其中,GJA3家族的致病突变是新的，家庭FTL是一种罕见的白内障综合征。这些家族性突变显示与受影响的个体完全共分离，不存在未受影响的家庭成员或100个对照。几种生物信息学预测工具也支持这些突变的可能致病性。
结论：我们的发现扩展了先天性白内障相关基因的突变和表型谱，为先天性白内障的发病机制提供了线索。这些数据也证明了NGS技术对于先天性白内障患者的分子诊断的重要性。
