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

Genes (Basel). 2022 Dec 14;13(12):2364. doi: 10.3390/genes13122364.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cataract* / congenital
  • DNA Copy Number Variations
  • Exome Sequencing
  • Humans
  • Hypogonadism* / diagnosis
  • Hypogonadism* / genetics
  • Male
  • Microcephaly* / genetics
  • Mutation
  • rab3 GTP-Binding Proteins / genetics


  • rab3 GTP-Binding Proteins
  • RAB3GAP1 protein, human

Supplementary concepts

  • Warburg Sjo Fledelius syndrome

Grants and funding

This study was supported by the National Key R&D Program of China, grant number: 2020YFC2008200, the Guangdong Basic and Applied Basic Research Foundation, grant number 2022A1515012102, and the Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Plan, grant number: 2022E02052.