caa a22 4500 397574045 CHVBK 20180308164849.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/hmg/5.4.433 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.4.433 Predominance of Null Mutations in Ataxia-Telangiectasia [Elektronische Daten] [Shlomit Gilad, Rami Khosravi, Dganit Shkedy, Tamar Uziel, Yael Ziv, Kinneret Savitsky, Galit Rotman, Sara Smith, Luciana Chessa, Timothy J. Jorgensen, Reli Harnik, Moshe Frydman, Ozden Sanal, Sima Portnoi, Zipora Goldwicz, N. G. J. Jaspers, Richard A. Gatti, Gilbert Lenoir, Martin F. Lavin, Kouichi Tatsumi, Rolf D. Wegner, Yosef Shiloh, Anat Bar-Shira] Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a PI 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the PI 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T. © 1996 Oxford University Press Gilad Shlomit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Khosravi Rami Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Shkedy Dganit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Uziel Tamar Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Ziv Yael Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Savitsky Kinneret Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Rotman Galit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Smith Sara Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Chessa Luciana Dipartimento di Medicina Sperimentale, Università Degli Studi di Roma ‘La Sapienza', 00161 Roma, Italy aut Jorgensen Timothy J. Department of Radiation Medicine, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington DC 20007-2197, USA aut Harnik Reli Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Frydman Moshe Institute of Human Genetics, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel aut Sanal Ozden Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey aut Portnoi Sima Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Goldwicz Zipora Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Jaspers N. G. J. Department of Cell Biology and Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands aut Gatti Richard A. Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90024, USA aut Lenoir Gilbert Laboratoire de Génétique JE 382, Université Claude Bernard, 69373 Lyon Cedex 08, France aut Lavin Martin F. Queensland Institute of Medical Research, Herston, Qld 4006, Australia aut Tatsumi Kouichi Department of Molecular Oncology, Kyoto University Faculty of Medicine, Kyoto 608, Japan aut Wegner Rolf D. Institut fur Humangenetik, Medizinische Fakultät der Humboldt-Universitat zu Berlin, D-14059 Berlin, Germany aut Shiloh Yosef Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Bar-Shira Anat Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut Human Molecular Genetics Oxford University Press 5/4(1996-04), 433-439 0964-6906 5:4<433 1996 5 hmg https://doi.org/10.1093/hmg/5.4.433 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.4.433 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gilad Shlomit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Khosravi Rami Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Shkedy Dganit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Uziel Tamar Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Ziv Yael Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Savitsky Kinneret Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Rotman Galit Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Smith Sara Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Chessa Luciana Dipartimento di Medicina Sperimentale, Università Degli Studi di Roma ‘La Sapienza', 00161 Roma, Italy aut NATIONALLICENCE 700 1- Jorgensen Timothy J. Department of Radiation Medicine, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington DC 20007-2197, USA aut NATIONALLICENCE 700 1- Harnik Reli Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Frydman Moshe Institute of Human Genetics, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel aut NATIONALLICENCE 700 1- Sanal Ozden Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey aut NATIONALLICENCE 700 1- Portnoi Sima Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Goldwicz Zipora Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Jaspers N. G. J. Department of Cell Biology and Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Gatti Richard A. Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90024, USA aut NATIONALLICENCE 700 1- Lenoir Gilbert Laboratoire de Génétique JE 382, Université Claude Bernard, 69373 Lyon Cedex 08, France aut NATIONALLICENCE 700 1- Lavin Martin F. Queensland Institute of Medical Research, Herston, Qld 4006, Australia aut NATIONALLICENCE 700 1- Tatsumi Kouichi Department of Molecular Oncology, Kyoto University Faculty of Medicine, Kyoto 608, Japan aut NATIONALLICENCE 700 1- Wegner Rolf D. Institut fur Humangenetik, Medizinische Fakultät der Humboldt-Universitat zu Berlin, D-14059 Berlin, Germany aut NATIONALLICENCE 700 1- Shiloh Yosef Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 700 1- Bar-Shira Anat Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/4(1996-04), 433-439 0964-6906 5:4<433 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford