Warburg Micro Syndrome 1 due to Segmental Paternal Uniparental Isodisomy of Chromosome 2 Detected by Whole-Exome Sequencing and Homozygosity Mapping

Creative Commons License

Sezer A., Kayhan G., Koc A., Ergün M. A., Perçin F. E.

CYTOGENETIC AND GENOME RESEARCH, vol.160, no.6, pp.309-315, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 160 Issue: 6
  • Publication Date: 2020
  • Doi Number: 10.1159/000509214
  • Journal Name: CYTOGENETIC AND GENOME RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.309-315
  • Gazi University Affiliated: Yes

Abstract

Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by microcephaly, cortical dysplasia, intellectual disability, ocular abnormalities, spastic diplegia, and microgenitalia. WARBM has 4 subtypes arising from pathogenic variants in 4 genes (RAB18,RAB3GAP1,RAB3GAP2, andTBC1D20). Here, we report on a patient with a homozygous pathogenic c.665delC (p.Pro222HisfsTer30) variant in theRAB3GAP1gene identified by whole-exome sequencing (WES) analyses. Only his father was a heterozygous carrier, and homozygosity mapping analysis of the WES data revealed large loss-of-heterozygosity regions in both arms of chromosome 2, interpreted as uniparental isodisomy. This uniparental disomy pattern could be due to paternal meiosis I nondisjunction because of the preserved heterozygosity in the pericentromeric region. This report provides novel insights, including a rare form of UPD, usage of homozygosity mapping analysis for the evaluation of isodisomy, and the first reported case of WARBM1 as a result of uniparental isodisomy.