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.

Keywords

AutoimmunityPhenotypeHaploinsufficiencyGeneticsBiologyLeucine zipperForkhead Transcription FactorsImmunologyGenePositional cloningImmune systemRegulation of gene expressionTranscription factor

MeSH Terms

Amino Acid SequenceAutoimmune DiseasesBase SequenceCell DifferentiationDNA Mutational AnalysisDiabetes MellitusType 1FemaleFood HypersensitivityForkhead Transcription FactorsGenetic LinkageHaplotypesHumansLeucine ZippersMaleMolecular Sequence DataMutationNuclear ProteinsPedigreeProtein StructureTertiaryRNA Splice SitesSequence AlignmentSequence HomologyAmino AcidSyndromeTh2 CellsTranscription FactorsX Chromosome

Affiliated Institutions

Related Publications

Publication Info

Year
2000
Type
article
Volume
106
Issue
12
Pages
R75-R81
Citations
918
Access
Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

918
OpenAlex
23
Influential
738
CrossRef

Cite This

Talal A. Chatila, Frank Blaeser, Nga Ho et al. (2000). JM2, encoding a fork head–related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome. Journal of Clinical Investigation , 106 (12) , R75-R81. https://doi.org/10.1172/jci11679

Identifiers

DOI
10.1172/jci11679
PMID
11120765
PMCID
PMC387260

Data Quality

Data completeness: 86%