Immune deficiencies, infection, and systemic immune disordersMorbidity and mortality from ataxia-telangiectasia are associated with ATM genotype
Section snippets
Diagnosis
ATM was genotyped in patients with 3 or more of the following: ataxia, oculocutaneous telangiectasia, recurrent infections, low serum levels of IgA, high serum levels of α-fetoprotein (≥10-fold the upper limit of normal), or A-T karyotype abnormalities (≥4% of metaphase lymphocytes with translocations at 7p14, 7q35, 14q11, 14q32, 2p12, or 22q11, as described in 1982).8 When no blood samples were available from pediatric patients or their parents, making analysis of ATM impossible, A-T was
Diagnosis and sociodemographic characteristics
From June 2006 to September 2007, 242 diagnoses of A-T were confirmed according to the described diagnostic criteria; 240 patients born from 1954 to 2005 were enrolled in the cohort (2 patients declined to participate). A-T was diagnosed based on clinical, laboratory, and molecular criteria for 76.7% (184/240) of the patients and based on clinical and laboratory criteria for only 23.3% (56/240) of the patients. In the latter group, in addition to ataxia, 96.4% (54/56) of the patients presented
Discussion
We have associated morbidity and mortality from A-T with the type of mutation in ATM using data from 240 patients. Analysis of this cohort indicated that time to diagnosis decreased from 1954 to 2007, possibly because of increasing knowledge about the disease and the availability of karyotype analysis in 1982 and ATM sequence analysis in 1997. Despite these advances and the fact that patients are almost always given a diagnosis of A-T at teaching hospitals because of the rarity and complexity
References (28)
- et al.
Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients
Pediatr Neurol
(2007) - et al.
Immunodeficiency and infections in ataxia-telangiectasia
J Pediatr
(2004) - et al.
Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to activation-induced cytidine deaminase deficiency
Clin Immunol
(2004) - et al.
Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study
Clin Immunol
(2002) Pulmonary complications of primary immunodeficiencies
Paediatr Respir Rev
(2004)- et al.
Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection
Pediatrics
(1958) - et al.
Localization of an ataxia-telangiectasia gene to chromosome 11q22-23
Nature
(1988) - et al.
A single ataxia telangiectasia gene with a product similar to PI-3 kinase
Science
(1995) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
Nat Rev Mol Cell Biol
(2008)- et al.
Cancer risks and mortality in heterozygous ATM mutation carriers
J Natl Cancer Inst
(2005)
The European internet-based patient and research database for primary immunodeficiencies: results 2004-06
Clin Exp Immunol
The French national registry of primary immunodeficiency diseases
Clin Immunol
J Genet Hum
Evaluation of in silico splice tools for decision-making in molecular diagnosis
Hum Mutat
Cited by (119)
Somatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications
2023, Critical Reviews in Oncology/HematologyFunctional analysis of ATM variants in a high risk cohort provides insight into missing heritability
2022, Cancer GeneticsCitation Excerpt :The disease AT itself has a highly variable presentation, with variant AT coined for patients with mild symptoms [67]. Age of symptom onset and presentation are known to be influenced by the genotype of AT patients and whether activity of the ATM protein is retained [68–71]. Numerous case reports exist for such patients who are either diagnosed late or otherwise do not follow the natural history of AT, including patients with mild or missing symptoms as a result of a mutation with partial function [72–76].
Expression of a large coding sequence: Gene therapy vectors for Ataxia Telangiectasia
2023, Scientific Reports
Supported by Sophie and Yves Ayache, CEREDIH (French National Reference Center for Primary Immunodeficiencies), and INCa (National Cancer Institute of France).
Disclosure of potential conflict of interest: A. Fischer receives research support from CEREDIH. The rest of the authors have declared that they have no conflict of interest.
- ∗
Romain Micol is currently affiliated with Transgene, Centre d’Infectiologie Lyon Biopôle, Lyon, France.