Blood, 1 May 2001, Vol. 97, No. 9, pp. 2772-2776
IMMUNOBIOLOGY
Identical mutations in RAG1 or RAG2 genes
leading to defective V(D)J recombinase activity can cause either
T-B-severe combined immune deficiency or Omenn syndrome
Barbara Corneo,
Despina Moshous,
Tayfun Güngör,
Nicolas Wulffraat,
Pierre Philippet,
Françoise Le Deist,
Alain Fischer, and
Jean-Pierre de Villartay
From the Dèveloppement Normal et
pathologique du Système Immunitaire, Hôpital Necker Enfants
Malades, Paris, France; Division of Immunology/Haematology, University
Children's Hospital, Zurich, Switzerland; Pediatric Immunology,
Children's Hospital, Utrecht, The Netherlands; and Division of
Pediatric, Immuno-hematology, C. H. St Joseph-Espèrance,
Montegnèe-Liège, Belgium.
Omenn syndrome (OS) is an inherited disorder characterized by an
absence of circulating B cells and an infiltration of the skin and the
intestine by activated oligoclonal T lymphocytes, indicating that a
profound defect in the lymphoid developmental program could be
accountable for this condition. Inherited mutations in either the
recombination activating genes RAG1 or
RAG2, resulting in partial V(D)J recombinase activity, were
shown to be responsible for OS. This study reports on the
characterization of new RAG1/2 gene mutations in a series
of 9 patients with OS. Given the occurrence of the same mutations in
patients with T-B-severe combined immune deficiency or OS on 3 separate occasions, the proposal is made that an additional factor may
be required in certain circumstances for the development of the Omenn
phenotype. The nature of this factor is discussed.
