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

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Abstract

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.

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Acknowledgments

We are indebted to the families for their participation in this study. We thank Mrs Susanne Rothe for the excellent technical assistance.

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Authors and Affiliations

  1. Institut für Medizinische Genetik und Humangenetik, Charité—Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Ilja Demuth, Véronique Dutrannoy, Heidemarie Neitzel, Luitgard M. Graul-Neumann, Martin Digweed, Karl Sperling & Raymonda Varon

  2. The Berlin Aging Study II; Research Group on Geriatrics, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Ilja Demuth

  3. Medical Genetics Division, Neurogenetics Clinics, University of São Paulo, São Paulo, Brazil

    Wilson Marques Jr & Charles Marques Lourenco

  4. Department of Human Genetics, University of Würzburg, Biozentrum am Hubland, 97074, Würzburg, Germany

    Detlev Schindler

  5. Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry, 1, Dr. Lyuben Roussev Street, 1113, Sofia, Bulgaria

    Petja S. Dimova & Veneta Bojinova

  6. Department of Medical Genetics, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland

    Krystyna H. Chrzanowska

  7. Department of Microbiology and Immunology, The Children’s Memorial Health Institute, Warsaw, Poland

    Hanna Gregorek

  8. DRK Kliniken Berlin Westend, Children’s Hospital, Berlin, Germany

    Arpad von Moers

  9. Centrum für Chronische Immunodefizienz; Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstrasse 1, 79106, Freiburg, Germany

    Ilka Schulze

  10. Department of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-St. 1, 30625, Hannover, Germany

    Marion Nicke & Thilo Dörk

  11. Department of Medical Genetics, Dokuz Eylul University, 35330, Izmir, Turkey

    Elcin Bora & Tufan Cankaya

  12. Medical and Health Science Center, Institute of Paediatrics, University of Debrecen, 4012, Debrecen, Nagyerdei krt. 98, Hungary

    Éva Oláh, Csongor Kiss, Beáta Bessenyei & Katalin Szakszon

  13. Children’s Hospital of the University of Graz, Auenbruggerplatz 30, A 8036, Graz, Austria

    Ursula Gruber-Sedlmayr

  14. Institute of Human Genetics, Medical University of Graz, Harrachg. 21/8, 8010, Graz, Austria

    Peter Michael Kroisel & Sigrun Sodia

  15. Institute of Human Genetics, Heinrich Heine University, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Timm O. Goecke

  16. Servico de Genética Médica, Hospital Pediátrico de Coimbra, Av. Bissaya Barreto, 3000-076, Coimbra, Portugal

    Joaquim de Sá

Authors
  1. Ilja Demuth
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  2. Véronique Dutrannoy
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  3. Wilson Marques Jr
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  4. Heidemarie Neitzel
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  5. Detlev Schindler
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  6. Petja S. Dimova
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  7. Krystyna H. Chrzanowska
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  8. Veneta Bojinova
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  9. Hanna Gregorek
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  10. Luitgard M. Graul-Neumann
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  11. Arpad von Moers
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  12. Ilka Schulze
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  13. Marion Nicke
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  14. Elcin Bora
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  15. Tufan Cankaya
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  16. Éva Oláh
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  17. Csongor Kiss
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  18. Beáta Bessenyei
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  19. Katalin Szakszon
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  20. Ursula Gruber-Sedlmayr
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  21. Peter Michael Kroisel
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  22. Sigrun Sodia
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  23. Timm O. Goecke
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  24. Thilo Dörk
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  25. Martin Digweed
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  26. Karl Sperling
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  27. Joaquim de Sá
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  28. Charles Marques Lourenco
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  29. Raymonda Varon
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Corresponding author

Correspondence to Ilja Demuth.

Additional information

Ilja Demuth and Véronique Dutrannoy contributed equally to this work.

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Demuth, I., Dutrannoy, V., Marques, W. et al. New mutations in the ATM gene and clinical data of 25 AT patients. Neurogenetics 12, 273–282 (2011). https://doi.org/10.1007/s10048-011-0299-0

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