Abstract：
OBJECTIVE: Bilateral pediatric cataract (BPC) is one of the most common causes of childhood visual impairment and blindness worldwide. A significant percentage of pediatric cataracts are caused by genetic alterations. We aim to characterize the set of genes and variants that cause BPC in the Israeli and Palestinian populations and to assess genotype-phenotype correlation.
METHODS: Retrospective study in a multidisciplinary center for visual impairment, located in a tertiary medical center. Medical charts of families who underwent genetic counseling because of BPC in a family member were reviewed. Clinical characteristics and genetic tests results were obtained from medical records of affected subjects.
RESULTS: Twenty-two families (47 patients) underwent genetic counseling and completed genetic testing. Causative variants were identified in 18/22 (81.8%) of the families, including 3 novel variants. Genetic testing used included mainly panel for congenital cataracts and whole exome sequencing. Eleven families performed genetic testing with the intention of future pregnancy planning. Main causative genes identified were crystalline genes followed by transcription factor genes. BCOR gene variants were associated with persistent fetal vasculature (PFV) cataract in two of three families.
CONCLUSIONS: Combined molecular techniques are useful in identifying variants causing pediatric cataracts and showed a high detection rate in our population. BCOR gene variants might be associated with PFV type of cataracts. The study of pathogenic variants may aid in family planning and prevention of pediatric cataracts in future pregnancies. Additionally, in certain cases, it assists in diagnosing non-suspected syndromic types of pediatric cataracts.
METHODS: Retrospective study in a multidisciplinary center for visual impairment, located in a tertiary medical center. Medical charts of families who underwent genetic counseling because of BPC in a family member were reviewed. Clinical characteristics and genetic tests results were obtained from medical records of affected subjects.
RESULTS: Twenty-two families (47 patients) underwent genetic counseling and completed genetic testing. Causative variants were identified in 18/22 (81.8%) of the families, including 3 novel variants. Genetic testing used included mainly panel for congenital cataracts and whole exome sequencing. Eleven families performed genetic testing with the intention of future pregnancy planning. Main causative genes identified were crystalline genes followed by transcription factor genes. BCOR gene variants were associated with persistent fetal vasculature (PFV) cataract in two of three families.
CONCLUSIONS: Combined molecular techniques are useful in identifying variants causing pediatric cataracts and showed a high detection rate in our population. BCOR gene variants might be associated with PFV type of cataracts. The study of pathogenic variants may aid in family planning and prevention of pediatric cataracts in future pregnancies. Additionally, in certain cases, it assists in diagnosing non-suspected syndromic types of pediatric cataracts.
摘要：
目的：双侧儿童白内障（BPC）是全球儿童视力障碍和失明的最常见原因之一。很大比例的小儿白内障是由遗传改变引起的。我们旨在表征在以色列和巴勒斯坦人口中引起BPC的一组基因和变体，并评估基因型-表型相关性。
方法：在多学科中心进行的回顾性研究，位于三级医疗中心。回顾了由于家庭成员中的BPC而接受遗传咨询的家庭的医学图表。从受影响受试者的医疗记录中获得临床特征和遗传测试结果。
结果：22个家庭（47名患者）接受了遗传咨询并完成了基因检测。在18/22（81.8%）的家族中发现了致病变异，包括3个新颖的变体。使用的基因检测主要包括先天性白内障小组和整个外显子组测序。11个家庭进行了基因检测，旨在制定未来的怀孕计划。鉴定出的主要致病基因是晶体基因，其次是转录因子基因。在三个家庭中的两个家庭中，BCOR基因变异与持续性胎儿血管系统（PFV）白内障有关。
结论：联合分子技术可用于鉴定引起小儿白内障的变异，并在我们人群中显示出较高的检出率。BCOR基因变异可能与PFV型白内障有关。致病变异的研究可能有助于计划生育和预防将来怀孕的小儿白内障。此外,在某些情况下,它有助于诊断非疑似综合征型小儿白内障。
方法：在多学科中心进行的回顾性研究，位于三级医疗中心。回顾了由于家庭成员中的BPC而接受遗传咨询的家庭的医学图表。从受影响受试者的医疗记录中获得临床特征和遗传测试结果。
结果：22个家庭（47名患者）接受了遗传咨询并完成了基因检测。在18/22（81.8%）的家族中发现了致病变异，包括3个新颖的变体。使用的基因检测主要包括先天性白内障小组和整个外显子组测序。11个家庭进行了基因检测，旨在制定未来的怀孕计划。鉴定出的主要致病基因是晶体基因，其次是转录因子基因。在三个家庭中的两个家庭中，BCOR基因变异与持续性胎儿血管系统（PFV）白内障有关。
结论：联合分子技术可用于鉴定引起小儿白内障的变异，并在我们人群中显示出较高的检出率。BCOR基因变异可能与PFV型白内障有关。致病变异的研究可能有助于计划生育和预防将来怀孕的小儿白内障。此外,在某些情况下,它有助于诊断非疑似综合征型小儿白内障。
