A genomic deletion encompassing CRYBB2-CRYBB2P1 is responsible for autosomal recessive congenital cataracts

Bushra Irum; Firoz Kabir; Nadav Shoshany; Shahid Y Khan; Bushra Rauf; Muhammad Asif Naeem; Tanveer A Qaiser; Sheikh Riazuddin; J Fielding Hejtmancik; S Amer Riazuddin

doi:10.1038/s41439-022-00208-7

A genomic deletion encompassing CRYBB2-CRYBB2P1 is responsible for autosomal recessive congenital cataracts

Hum Genome Var. 2022 Sep 8;9(1):31. doi: 10.1038/s41439-022-00208-7.

Authors

Bushra Irum^#^{1

2}, Firoz Kabir^#¹, Nadav Shoshany³, Shahid Y Khan¹, Bushra Rauf^{1

2}, Muhammad Asif Naeem², Tanveer A Qaiser⁴, Sheikh Riazuddin^{2

4}, J Fielding Hejtmancik³, S Amer Riazuddin⁵

Affiliations

¹ The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
² National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, 53700, Pakistan.
³ Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
⁴ Jinnah Burn & Reconstructive Surgery Centre, Jinnah Hospital, Lahore, 54550, Pakistan.
⁵ The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. riazuddin@jhmi.edu.

^# Contributed equally.

Abstract

Here we report a consanguineous Pakistani family with multiple affected individuals with autosomal recessive congenital cataract (arCC). Exclusion analysis established linkage to chromosome 22q, and Sanger sequencing coupled with PCR-based chromosome walking identified a large homozygous genomic deletion. Our data suggest that this deletion leads to CRYBB2-CRYBB2P1 fusion, consisting of exons 1-5 of CRYBB2 and exon 6 of CRYBB2P1, the latter of which harbors the c.463 C > T (p.Gln155*) mutation, and is responsible for arCC.