Mutation screening by whole exome sequencing in pediatric cases with isolated cataract
Project no. 20821 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
Congenital cataracts are one of the preventable causes of childhood blindness. Approximately 1/10 of childhood blindness is caused by congenital cataracts. The clinic and genetics of congenital cataracts are heterogeneous and have different classifications. These classifications are made according to etiology, formation periods, morphologies and types of occurrence; according to its etiology: idiopathic and hereditary, according to the period of occurrence: congenital, infantile and juvenile, according to morphology: total and partial, according to the types of occurrence: primary and secondary. Approximately 1/3 of cataracts are inherited autosomal dominant (AD) which is the most common, and followed by autosomal recessive (OR) and X-linked. Objective: This study aimed to define the etiology of congenital cataract (CC) in patients which is not associated with a known metabolic disease and genetic syndrome, by using the array whole exome sequencing (WES). Materials and Methods: Between December 2019 and February 2021, patients between the ages of 0-18, who were not associated with a known metabolic disease or genetic syndrome, who had no additional eye anomalies, healthy and who were diagnosed with isolated congenital cataract, were included this study at Ege University Pediatric Genetic Diseases and Pediatric Metabolism Department. Based on these data, a case report form was created and filled. Blood was drawn from the patients for WES examination and the results were investigated. Results: There was consanguinity between the parents of 8 of 11 patients. There was no additional eye anomaly in our patients. Of the 10 patients diagnosed with isolated CC, 9 (90%) had bilateral cataract and one (10%) had unilateral cataract. Nuclear type cataract was detected in 10 (90.9%) of the patients, and polar type cataract was detected in one (9.09%) of the patients. In our study, 5 novel gene mutations associated with isolated CC WHİCH HAVE NOT BEEN previously identified were found. The RAB3GAP1 gene mutation associated with Warburg Micro syndrome has also not been identified TO DATE AS WELL. Mutations were found in 6 genes, 5 of which were associated with isolated CC, and one was identified. There was consanguinity between the parents in 6 patients and no consanguinity in one patient (63.6%). A mutation in the RAB3GAP1 gene Warburg Micro syndrome was found in one of our patients. Among the mutations, one of 7 patients (14.3%) had a mutation in the CRYGD gene, which is was from the crystalline group. This is the most common causative gene mutation in the formation of isolated cataracts. In the remaining 6 patients, gene mutations causing rare isolated CC were found as; HSF4 (Heat Shock Factor 4) gene mutation with transcription factor gene mutation in two (28.6%) patients, one (14.3%) CTBP2 gene mutation (C-terminal-binding protein) in one patient, FYCO1 (FYVE and coiled coil domain containing 1) gene mutation in one (14.3%) patient, VIM (Vimentin) gene mutation in one (14.3%) and WFS1 (Wolfram syndrome 1) gene mutation in last patient. Mutations were like these: c.463C> T in CRYGD gene, c.2272G> T, c.22A> T in CTBP2 gene, c.965dup in HSF4 gene, c.1360G> A in VIM gene, c.3330C> A in FYCO1 gene, c.1294C> G. Transition patterns of the gene mutations found were AD in 6 patients (85.7%) and AR in one patient (14.2%). Conclusion: NGS examination method seems to be an important option in defining the etiology of genetic heterogeneous diseases such as CC.