Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

  • Nat Genet. 2005 Mar;37(3):221-3. doi: 10.1038/ng1517.
Irene A Aligianis  1 ,  Colin A Johnson ,  Paul Gissen ,  Dongrong Chen ,  Daniel Hampshire ,  Katrin Hoffmann ,  Esther N Maina ,  Neil V Morgan ,  Louise Tee ,  Jenny Morton ,  John R Ainsworth ,  Denise Horn ,  Elisabeth Rosser ,  Trevor R P Cole ,  Irene Stolte-Dijkstra ,  Karen Fieggen ,  Jill Clayton-Smith ,  André Mégarbané ,  Julian P Shield ,  Ruth Newbury-Ecob ,  William B Dobyns ,  John M Graham Jr ,  Klaus W Kjaer ,  Mette Warburg ,  Jacqueline Bond ,  Richard C Trembath ,  Laura W Harris ,  Yoshimi Takai ,  Stefan Mundlos ,  David Tannahill ,  C Geoffery Woods ,  Eamonn R Maher
Affiliations
  • 1. Section of Medical and Molecular Genetics, University of Birmingham, Birmingham, B15 2TT, UK.
PMID: 15696165 DOI: 10.1038/ng1517
Abstract

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and Hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.