New mutations in the ATM gene and clinical data of 25 AT patients

• Published in: Neurogenetics Vol. 12; no. 4; pp. 273 - 282
• Main Authors: Demuth, Ilja, Dutrannoy, Véronique, Marques, Wilson, Neitzel, Heidemarie, Schindler, Detlev, Dimova, Petja S., Chrzanowska, Krystyna H., Bojinova, Veneta, Gregorek, Hanna, Graul-Neumann, Luitgard M., von Moers, Arpad, Schulze, Ilka, Nicke, Marion, Bora, Elcin, Cankaya, Tufan, Oláh, Éva, Kiss, Csongor, Bessenyei, Beáta, Szakszon, Katalin, Gruber-Sedlmayr, Ursula, Kroisel, Peter Michael, Sodia, Sigrun, Goecke, Timm O., Dörk, Thilo, Digweed, Martin, Sperling, Karl, de Sá, Joaquim, Lourenco, Charles Marques, Varon, Raymonda
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2011; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; Adolescent; Adult; Ataxia Telangiectasia - genetics; Ataxia telangiectasia mutated protein; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cerebellum; Child; Child, Preschool; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Clinical outcomes; Data processing; Degeneration; DNA damage; DNA Mutational Analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetics of eukaryotes. Biological and molecular evolution; Genomic instability; Haplotypes; Hereditary diseases; Human Genetics; Humans; Immunodeficiency; Male; Medical genetics; Medical sciences; Missense mutation; Molecular and cellular biology; Molecular Medicine; Mutation; Neurosciences; Original Article; Patients; Phenotype; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Radiosensitivity; RNA Splicing; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Vertebrates: nervous system and sense organs; Mutation screening; Ataxia telangiectasia; ATM; Human; Immunopathology; Skin disease; Nervous system diseases; Patient; Cardiovascular disease; Medical screening; Genetic disease; Vascular disease; Screening; Neurology; Eye disease; Gene; Genetics; Mutation
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s10048-011-0299-0

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM , encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage. Truncating and splice site mutations in ATM have been found in most patients with the classical AT phenotype. Here we report of our extensive ATM mutation screening on 25 AT patients from 19 families of different ethnic origin. Previously unknown mutations were identified in six patients including a new homozygous missense mutation, c.8110T>C (p.Cys2704Arg), in a severely affected patient. Comprehensive clinical data are presented for all patients described here along with data on ATM function generated by analysis of cell lines established from a subset of the patients.