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J Clin Invest. 2000 Dec;106(12):R75-81.

JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome.

Author information

1
Department of Pediatrics, and. Department of Pathology and Immunology and the Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. chatila@kids.wustl.edu

Abstract

X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity, particularly early-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.

PMID:
11120765
PMCID:
PMC387260
DOI:
10.1172/JCI11679
[Indexed for MEDLINE]
Free PMC Article

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