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Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease


We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency, an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease. This is the first report of the involvement of a nuclear body protein in a human primary immunodeficiency and of high-penetrance genetic mutations in hepatic veno-occlusive disease.

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Figure 1: SP110 mapping and mutation analysis.
Figure 2: Functional consequences of SP110 mutations.

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We thank the families with VODI for their participation, D. Reeves for histopathological interpretation and the financial support of the New South Wales Health Research Infrastructure Grant, the Sydney Children's Hospital Foundation, the Australian National Health and Medical Research Council (NHMRC), an NHMRC postgraduate research scholarship (T.R.), the US National Institutes of Health (J.W. and G.B.M.) and the Deutsche Forschungsgemeinschaft (U.S.).

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Correspondence to Tony Roscioli.

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Roscioli, T., Cliffe, S., Bloch, D. et al. Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease. Nat Genet 38, 620–622 (2006).

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