Abstract
Congenital cytomegalovirus brain infection without symptoms at birth can cause a static encephalopathy with characteristic patterns of brain abnormalities. Here we show that loss-of-function mutations in the gene encoding the RNASET2 glycoprotein lead to cystic leukoencephalopathy, an autosomal recessive disorder with an indistinguishable clinical and neuroradiological phenotype. Congenital cytomegalovirus infection and RNASET2 deficiency may both interfere with brain development and myelination through angiogenesis or RNA metabolism.
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Acknowledgements
We thank the subjects and their families for participating in the study, C. Becker, L. Florin, M. Grapp, R. Hitt, J. Landgrebe and G. Nürnberg for expert technical assistance, and A. Fuchs, T.V.O. Hansen, R. Sedlmeier, O. Shoseyov and G. Tretter for collaborative efforts. This work has been supported by the Deutsche Forschungsgemeinschaft Grant GA354/6-1 (J.G. and M.H.) and the Bundesministerium für Bildung and Forschung (BMBF) through the German Leukodystrophy Network (M.H. and J.S.).
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M.H.: subject classification, clinical study, linkage analysis, mapping, mutational screening, writing of the manuscript; S.D.: RTQ-PCR, protein expression, immunoblot; A.O., J.S.: mutational screening; J.K.: mutational screening, protein expression; V.E., A.K., M.M.-G., M.M., D.R.: subject classification, clinical samples and data; R.K., S.T., R.S.: yeast studies, protein expression, enzyme assays; L.O.: microarray expression experiments; F.R., H.T., P.N.: linkage analysis and mapping; J.G.: study design, supervision of clinical, molecular and functional study, writing of the manuscript.
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Supplementary Tables 1–4, Supplementary Figures 1–11 and Supplementary Methods (PDF 3187 kb)
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Henneke, M., Diekmann, S., Ohlenbusch, A. et al. RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection. Nat Genet 41, 773–775 (2009). https://doi.org/10.1038/ng.398
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DOI: https://doi.org/10.1038/ng.398
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