title: CD3G gene defects in familial autoimmune thyroiditis.
abstract: The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαβ+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.
authors.affiliation: Division of Immunology and Allergy, Konya Training and Research Hospital, Konya, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Gokturk
authors.forename: S
authors.initials: S
authors.lastname: Keles
authors.forename: M
authors.initials: M
authors.lastname: Kirac
authors.forename: H
authors.initials: H
authors.lastname: Artac
authors.forename: H
authors.initials: H
authors.lastname: Tokgoz
authors.forename: S N
authors.initials: SN
authors.lastname: Guner
authors.forename: U
authors.initials: U
authors.lastname: Caliskan
authors.forename: Z
authors.initials: Z
authors.lastname: Caliskaner
authors.forename: M
authors.initials: M
authors.lastname: van der Burg
authors.forename: J
authors.initials: J
authors.lastname: van Dongen
authors.forename: N V
authors.initials: NV
authors.lastname: Morgan
authors.forename: I
authors.initials: I
authors.lastname: Reisli
mesh_terms: D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics; D000974:Antibodies, Antinuclear / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics*; D002648:Child; D003876:Dermatitis, Atopic / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D019693:Hepatitis, Autoimmune / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D009402:Nephrosis, Lipoid / Q000235:genetics; D010375:Pedigree; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D014820:Vitiligo / Q000235:genetics; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D007073:Immunoglobulin E