title: The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents.
abstract: Eleven Norwegian patients (aged 2-33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0.23 (0.05-0.41) g/l versus 0.91 (0.58-1.26) g/l in the other patients (P = 0.002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0.9 (0.4-1.4) U/ml, while normal levels were found in their parents 11.1 (8.7-13.4) U/ml (P < 0.001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0.85, P = 0.001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23-64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.
authors.affiliation: Department of Paediatrics, Rikshospitalet University Hospital, Oslo, Norway. asbjorg.stray-pedersen@rikshospitalet.no
authors.forename: A
authors.initials: A
authors.lastname: Stray-Pedersen
authors.forename: T
authors.initials: T
authors.lastname: Jónsson
authors.forename: A
authors.initials: A
authors.lastname: Heiberg
authors.forename: C R
authors.initials: CR
authors.lastname: Lindman
authors.forename: E
authors.initials: E
authors.lastname: Widing
authors.forename: I S
authors.initials: IS
authors.lastname: Aaberge
authors.forename: A L
authors.initials: AL
authors.lastname: Borresen-Dale
authors.forename: T G
authors.initials: TG
authors.lastname: Abrahamsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000235:genetics*; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D017098:IgA Deficiency / Q000150:complications; D007072:Immunoglobulin D / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D007136:Immunoglobulins / Q000097:blood / Q000235:genetics*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009154:Mutation; D010290:Parents; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015703:Antigens, CD; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007136:Immunoglobulins