Investigation of molecular ethiology with new generation sequence in congenital / developmental cataracts that cannot be associated with metabolic diseases and syndromes

Taylan Şekeroğlu H., Investigation of the Molecular Etiology of Congenital/Developmental Cataract Which Can Not Be Attributed to Known Metabolic Diseases or Syndromes by Next Generation Sequencing, Hacettepe University, Graduate School of Health Sciences, Doctor of Philosophy Thesis in Genetics, Ankara, 2020. The aim of the study was to identify the molecular etiology in patients with congenital/developmental cataract which can not be attributed to known metabolic diseases or syndromes by next generation sequencing. A total of four patients (three girls and one boy) who had isolated bilateral cataract were enrolled in the study after detailed genetic and metabolic evaluation. Two patients had nuclear, one patient had total and one patient had combined lamellar and sutural cataract. All patients underwent bilateral lensectomy and anterior vitrectomy. One family had consanguinity. DNA (Deoxyribonucleic Acid) was extracted from peripheral blood of probands and selected affected individuals in the family. Whole exome sequencing (WES) was performed by IonProton® technology. The results were confirmed by Sanger sequencing. Heterozygous c.215+1G>A mutation in CRYBA1 was detected in one patient, heterozygous c.432C>G (p.Tyr144Ter) mutation in CRYGC was detected in one patient, heterozygous c.70A>C (p.Pro24Thr) mutation in CRYGD was detected in one patient and heterozygous c.466G>A (p.Gly156Arg) mutation in CRYBB3 was detected in one patient. All these mutations were also detected in selected affected individuals of the families and were located on the crystalline genes which have been previously reported to be associated with congenital cataract. The study highlights that crystalline genes should be considered in the first place when performing studies regarding the genetic etiology of the congenital cataract in our country and the implementation of WES as a useful technology in identifying the genetic basis of complex diseases such as congenital cataract. In addition, the present study has a unique property and is the first report of whole exome sequencing data in regard with congenital cataract in our country.