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


SEZER A. , KAYHAN G. , Koc A., ERGÜN M. A. , PERÇİN F. E.

CYTOGENETIC AND GENOME RESEARCH, cilt.160, sa.6, ss.309-315, 2020 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 160 Konu: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1159/000509214
  • Dergi Adı: CYTOGENETIC AND GENOME RESEARCH
  • Sayfa Sayıları: ss.309-315

Özet

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.