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Case Reports
. 2022 Dec 14;13(12):2364.
doi: 10.3390/genes13122364.

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

Qiwei Wang  1 , Tingfeng Qin  1 , Xun Wang  1 , Jing Li  1 , Xiaoshan Lin  1 , Dongni Wang  1 , Zhuoling Lin  1 , Xulin Zhang  1 , Xiaoyan Li  1 , Haotian Lin  1 , Weirong Chen  1
Affiliations
Case Reports

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

Qiwei Wang et al. Genes (Basel). .

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.

Keywords: RAB3GAP1; Warburg Micro syndrome; copy number variation; early diagnosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Anterior segment photographs of the patient with WARBM. (A) Anterior segment photograph using diffuse illumination of the right eye showing the persistent papillary membrane and lens fibrotic opacities. (B) Anterior segment photograph using diffuse illumination of the left eye, showing the persistent papillary membrane and lens fibrotic opacities. (C) Anterior segment photograph using direct focal illumination of the right eye showing the decreased thickness of the lens. (D) Anterior segment photograph using direct focal illumination of the left eye showing the decreased thickness of the lens. (Red arrow: lens fibrotic opacities).
Figure 2
Figure 2
Molecular finding of the Chinese Han families. (A) The boy was born to non-consanguineous unaffected parents. (B) The sanger sequence of the family members showing a novel heterozygous c.178_182del variant in the affected proband and his unaffected father. (C) Chromosome 2q21.3 deletion removing 4 of the 24 exons of RAB3GAP1 in the affected proband and his unaffected mother identified from whole exome sequencing data.
Figure 3
Figure 3
Schematic diagrams of RAB3GAP1. Cyan-blue: Rab3-GTPase-activating protein catalytic subunit; Red label: c.178_182del, p. Glu60IlefsTer3 variant; Grey label: chromosome 2q21.3 deletion removing 4 of the 24 exons of RAB3GAP1; dotted line: boundary of exons.
See this image and copyright information in PMC

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