Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome

Abstract

Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.

Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

“…More recently, Olfe et al have demonstrated CTLA-4 insufficiency due to a novel CTLA-4 deletion using ClinCNV ( German and Stephan, 2019 ; Olfe et al, 2023 ), further highlighting the synergy of CNV calling with WES analysis. Beyond the scope of autoimmune diseases, NGS techniques have also been extensively utilized in identifying causal variants (including CNVs) contributing to cancer ( van Dijk et al, 2014 ; Papp et al, 2021 ; Satam et al, 2023 ), congenital ( Lai et al, 2021 ; Li et al, 2022 ; Liu et al, 2022 ; Wang et al, 2022 ; Wu et al, 2022 ; Refeat et al, 2023 ), cardiovascular ( Hu et al, 2023 ) and hematological diseases ( Hassan et al, 2023 ).…”