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.
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Acknowledgements
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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Supplementary information
Supplementary Fig. 1
Expression of RAB3GAP/WARBM1 (Rab3-GAP p130 catalytic subunit) mRNA in the mouse embryo as assessed by in situ hybridisation. (PDF 1491 kb)
Supplementary Table 1
Fine mapping data for the affected individuals from families K1–K5. (PDF 91 kb)
Supplementary Table 2
Primer sequences of novel microsatellite markers used for linkage analysis. (PDF 41 kb)
Supplementary Table 3
Clinical data for the Micro families in this study not previously described in the literature. (PDF 70 kb)
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Aligianis, I., Johnson, C., Gissen, P. et al. Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. Nat Genet 37, 221–224 (2005). https://doi.org/10.1038/ng1517
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DOI: https://doi.org/10.1038/ng1517
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