Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype

Romain Micol; Lilia Ben Slama; Felipe Suarez; Loic Le Mignot; Julien Beaute; Nizar Mahlaoui; Catherine Dubois d'Enghien; Anthony Lauge; Janet Hall; Jerome Couturier; Louis Vallee; Bruno Delobel; Francois Rivier; Karine Nguyen; Thierry Billette de Villemeur; Jean-Louis Stephan; Pierre Bordigoni; Yves Bertrand; Nathalie Aladjidi; Jean-Michel Pedespan; Caroline Thomas; Isabelle Pellier; Michel Koenig; Olivier Hermine; Capucine Picard; Despina Moshous; Benedicte Neven; Fanny Lanternier; Stephane Blanche; Marc Tardieu; Marianne Debre; Alain Fischer; Dominique Stoppa-Lyonnet; CEREDIH Network

doi:10.1016/j.jaci.2011.03.052

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Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype

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Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype

Romain Micol, Lilia Ben Slama, Felipe Suarez, Loic Le Mignot, Julien Beaute, Nizar Mahlaoui, Catherine Dubois d'Enghien, Anthony Lauge, Janet Hall, Jerome Couturier, …

Journal of allergy and clinical immunology, Vol.128(2), pp.382-U400

01/08/2011

DOI: https://doi.org/10.1016/j.jaci.2011.03.052

PMID: 21665257

Résumé

Allergy

Immunology

Life Sciences & Biomedicine

Science & Technology

Background: Ataxia-telangiectasia (A-T) is a rare genetic disease caused by germline biallelic mutations in the ataxia-telangiectasia mutated gene (ATM) that result in partial or complete loss of ATM expression or activity. The course of the disease is characterized by neurologic manifestations, infections, and cancers. Objective: We studied A-T progression and investigated whether manifestations were associated with the ATM genotype. Methods: We performed a retrospective cohort study in France of 240 patients with A-T born from 1954 to 2005 and analyzed ATM mutations in 184 patients, along with neurologic manifestations, infections, and cancers. Results: Among patients with A-T, the Kaplan-Meier 20-year survival rate was 53.4%; the prognosis for these patients has not changed since 1954. Life expectancy was lower among patients with mutations in ATM that caused total loss of expression or function of the gene product (null mutations) compared with that seen in patients with hypomorphic mutations because of earlier onset of cancer (mainly hematologic malignancies). Cancer (hazard ratio, 2.7; 95% CI, 1.6-4.5) and respiratory tract infections (hazard ratio, 2.3; 95% CI, 1.4-3.8) were independently associated with mortality. Cancer (hazard ratio, 5.8; 95% CI, 2.9-11.6) was a major risk factor for mortality among patients with null mutations, whereas respiratory tract infections (hazard ratio, 4.1; 95% CI, 1.8-9.1) were the leading cause of death among patients with hypomorphic mutations. Conclusion: Morbidity and mortality among patients with A-T are associated with ATM genotype. This information could improve our prognostic ability and lead to adapted therapeutic strategies. (J Allergy Clin Immunol 2011;128:382-9.)

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Titre: Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype
Créateurs - sans rôle: Romain Micol - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Lilia Ben Slama - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Felipe Suarez - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Loic Le Mignot - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Julien Beaute - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Nizar Mahlaoui - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Catherine Dubois d'Enghien - Inst Curie Hop, Canc Genet Dept, Cytogenet Unit, Paris, France
Anthony Lauge - Inst Curie Hop, Canc Genet Dept, Cytogenet Unit, Paris, France
Janet Hall - Inst Curie Rech, INSERM, U830, Paris, France
Jerome Couturier - Inst Curie Hop, Canc Genet Dept, Cytogenet Unit, Paris, France
Louis Vallee - Univ Lille, CHRU, Pediat Neurol Unit, Childrens Dept, Lille, France
Bruno Delobel - Université de Lille
Francois Rivier - Univ Montpellier, Medecine UFR, F-34059 Montpellier, France
Karine Nguyen - CHU Timone Enfants, Dept Med Genet, Marseille, France
Thierry Billette de Villemeur - Univ Paris 06, Paris, France
Jean-Louis Stephan - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Pierre Bordigoni - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Yves Bertrand - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Nathalie Aladjidi - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Jean-Michel Pedespan - Univ Bordeaux 2, Pediat Neurol Dept, F-33076 Bordeaux, France
Caroline Thomas - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Isabelle Pellier - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Michel Koenig - ULP, Mol & Cellular Biol & Genet Inst, CNRS, INSERM, Illkirch Graffenstaden, France
Olivier Hermine - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Capucine Picard - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Despina Moshous - Hop Necker Enfants Malad, Pediat Immunohematol Dept, F-75743 Paris 15, France
Benedicte Neven - Hop Necker Enfants Malad, Pediat Immunohematol Dept, F-75743 Paris 15, France
Fanny Lanternier - Univ Paris 05, Hop Necker Enfants Malad, Necker Pasteur Infect Dis Ctr, Trop & Infect Dis Dept, Paris, France
Stephane Blanche - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Marc Tardieu - Hop Bicetre, AP HP, Le Kremlin Bicetre, France
Marianne Debre - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Alain Fischer - Hop Necker Enfants Malad, CEREDIH Network, French Natl Reference Ctr Primary Immunodeficienc, F-75743 Paris 15, France
Dominique Stoppa-Lyonnet - Paris Descartes Univ, Paris, France
CEREDIH Network
Détails de publication: Journal of allergy and clinical immunology, Vol.128(2), pp.382-U400
Éditeur: Elsevier
Nombre de pages: 9
Note de subvention: INCa (National Cancer Institute of France); Institut National du Cancer (INCA) France CEREDIH CEREDIH (French National Reference Center for Primary Immunodeficiencies) Sophie and Yves Ayache
Identifiants: 99158874909311
Unité académique: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Langue: English
Type de ressource: Journal article