Human Molecular Genetics, Vol 8, 2407-2413, Copyright © 1999 by Oxford University Press
O Brandau, V Schuster, M Weiss, H Hellebrand, FM Fink, A Kreczy, W Friedrich, B Strahm, C Niemeyer, BH Belohradsky and A Meindl
X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency,
which most often manifests itself after Epstein-Barr virus (EBV) infection.
The main clinical phenotypes include fulminant or fatal infectious
mononucleosis, dysgammaglobulinaemia and malignant lymphoma. We have
recently cloned the SH2D1A gene, which has been shown to be mutated in ~70%
of XLP patients. Now we report five novel SH2D1A mutations in patients from
five unrelated XLP families. No mutations were found in another three XLP
families. In three boys with early onset non-Hodgkin lymphoma (NHL) from
two unrelated families a deletion of SH2D1A exon 1 and a splice site
mutation were found, respectively. These patients did not show any
laboratory or clinical signs of a previous EBV infection. A fourth
EBV-uninfected and unrelated boy with a stop mutation in the SH2D1A gene
shows only signs of dysgammaglobulinaemia. Development of
dysgamma-globulinaemia and lymphoma without evidence of prior EBV infection
in four of our patients suggests that EBV is unrelated to these phenotypes,
in contrast to fulminant or fatal infectious mononucleosis. The role of
SH2D1A as a putative tumour suppressor gene remains to be investigated.
ARTICLES
Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP)
Department of Medical Genetics, LMU, 80336 M#nchen, Germany,
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