Large homozygous RAB3GAP1 gene microdeletion causes Warburg micro syndrome 1

Orphanet J Rare Dis. 2014 Oct 21:9:113. doi: 10.1186/s13023-014-0113-9.

Abstract

Warburg micro syndrome (WARBM) is a genetic heterogeneous disease characterized by microcephaly, intellectual disability, brain, ocular, and endocrine anomalies. WARBM1-4 can be caused by biallelic mutations of the RAB3GAP1 (RAB3 GTPase-activating protein 1), RAB3GAP2, RAB18 (RAS-associated protein RAB18), or TBC1D20 (TBC1 domain protein, member 20) gene, respectively. Here, we delineate the so far largest intragenic homozygous RAB3GAP1 microdeletion. Despite the size of the RAB3GAP1 gene deletion, the patient phenotype is mainly consistent with that of other WARBM1 patients, supporting strongly the theory that WARBM1 is caused by a loss of RAB3GAP1 function. We further highlight osteopenia as a feature of WARBM1.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Cataract / congenital*
  • Cataract / diagnosis
  • Cataract / genetics
  • Child
  • Child, Preschool
  • Cornea / abnormalities*
  • Female
  • Gene Deletion*
  • Homozygote*
  • Humans
  • Hypogonadism / diagnosis*
  • Hypogonadism / genetics*
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Microcephaly / diagnosis*
  • Microcephaly / genetics*
  • Optic Atrophy / diagnosis*
  • Optic Atrophy / genetics*
  • Pedigree
  • rab3 GTP-Binding Proteins / genetics*

Substances

  • RAB3GAP1 protein, human
  • rab3 GTP-Binding Proteins

Supplementary concepts

  • Warburg Sjo Fledelius syndrome