Format

Send to

Choose Destination
J Allergy Clin Immunol. 2011 Aug;128(2):382-9.e1. doi: 10.1016/j.jaci.2011.03.052. Epub 2011 Jun 12.

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

Collaborators (220)

Slama LB, Beauté J, Boileau J, Dudoit Y, Hilpert S, Mahlaoui N, de Vergnes N, Micol R, Obenga G, Heinz N, Korganow AS, Lutz P, Pasquali JL, Aladjidi N, Micheau M, Perel Y, Viallard JF, Bonnotte B, Briandet C, Couillault G, Legrand F, Rohrlich PS, Decaux O, Gandemer V, Grosbois B, Le Gall E, Berthou C, Lemoine P, Aaron L, Hoarau C, Lebranchu Y, Jaussaud R, Munzer M, Marie-Cardine A, Vannier JP, Jacquot S, Tron F, Fieschi C, Galicier L, Malphettes M, Leverger G, Ouchée-Charin M, Leblanc T, Baruchel A, Catherinot E, Coignard-Biehler H, Lanternier F, Chandesris O, Blanche S, Casanova JL, Debré M, Frange P, Moshous D, Mouy R, Neven B, Mouthon L, Amoura Z, Mathian A, Galanaud P, Lambotte O, Levy Y, Bernard F, Jeziorski E, Le Quellec A, Le Moing V, Jaccard A, Piguet C, Bordigoni P, Salmon A, Adoue D, Arlet P, Rubie H, Teira P, Hachulla E, Mazingue F, Barlogis V, Michel G, Schleinitz N, Deville A, Dulieu F, Monpoux F, Gardembas M, Pellier I, Bienvenu B, Boutard P, Hamidou M, Masseau A, Thomas C, Lassoued K, Marolleau JP, Pautard B, Royer B, Millot F, Roblot P, Demeocq F, Massot C, Sarrot-Reynauld F, Plantaz D, Bertrand Y, Kebaili K, Cozon G, Durieu I, Nove-Josserand R, Pavic M, Stephan JL, Donadieu J, Landais P, Lecuit M, Lortholary O, Picard C, Suarez F, Oksenhendler E, Hermine O, Fischer A, Kindle G, Gathmann B, Allani-Essid N, Altuzarra C, Alves C, Armari-Alla C, Aubourg P, Audic-Gerard F, Azulay JP, Barthez MA, Baumann-Morel C, Mansour LB, Bera O, Boespflug-Tanguy O, Borie D, Brichard B, Burglen L, Calvas P, Carriere JP, Cartault F, Casteleyn AS, Chabrol B, Chevalier MC, Coskun S, Croquette MF, Cuntz-Shadfar D, Curtillet C, Dahan K, Darteyre S, Delattre P, Delrue MA, Demeocq F, De La Fosse VD, Dollfus H, Dugast C, Durr A, Dusser A, Echenne B, Edery P, Evrard P, Ghamlouch SF, Flori E, Fraix V, Francannet C, Gautier E, Gerardin P, Goldenberg A, Graber D, Guillerlain G, Guillermet C, Guillot F, Hayat P, Heron-Longe B, Husson M, Ioos C, Vuillaume I, Jacquemont ML, Jeandidier E, Jonveaux P, Jouk PS, Journel H, Keren B, Lacombe D, Leguern E, Lobut JB, Mancini J, Martin-Coignard D, Mathieu S, Mathieu-Dramard M, Mauget M, Mellouli F, Moutard ML, Nguyen K, Olivier-Faivre L, Parent P, Pasquier L, Pellier F, Pellissier MC, Peter L, Philip N, Piette JC, Plouvier E, Prieur F, Rio M, Rochette J, Rohrlich PS, Roubertie A, Rousselet F, Routon MC, Sarda P, Saura R, Scares D, Servais L, Sicard-Mauclair C, Sigaudy S, Soares D, Sukno S, Sznajer Y, Thauvin-Robinet C, Thumerelle C, Till M, Toutain A, Veber F, Ville D, Ythier H, Zattara-Cannoni H.

Author information

1
CEREDIH, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, 75743 Paris Cedex 15, France. romain.micol@gmail.com

Abstract

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.

PMID:
21665257
DOI:
10.1016/j.jaci.2011.03.052
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center