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.
Bibliographical noteFunding Information:
We thank the families who helped with this research; many colleagues, particularly E.R. Roeder and C.J. Curry, for referring affected individuals; and the UK Birth Defects Foundation, the Wellcome Trust and Birmingham Women’s Hospital R&D Fund for financial support.
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