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| Predominance of null mutations in ataxia-telangiectasia |
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| Author(s): Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NGJ, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, BarShira A |
| Source: HUMAN MOLECULAR GENETICS Volume: 5 Issue: 4 Pages: 433-439 Published: APR 1996 |
| Times Cited: 189 References: 41 |
| Abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, AIM, 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 AIM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T. |
| Document Type: Article |
| Language: English |
Addresses:
1. TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN GENET, IL-69978 RAMAT AVIV, ISRAEL
2. UNIV ROMA LA SAPIENZA, DIPARTIMENTO MED SPERIMENTALE, I-00161 ROME, ITALY
3. GEORGETOWN UNIV, MED CTR, VINCENT T LOMBARDI CANC RES CTR, DEPT RADIAT MED, WASHINGTON, DC 20007 USA
4. CHAIM SHEBA MED CTR, INST HUMAN GENET, IL-52621 TEL HASHOMER, ISRAEL
5. HACETTEPE UNIV, FAC MED, DEPT PEDIAT, ANKARA 06100, TURKEY
6. ERASMUS UNIV ROTTERDAM, DEPT GENET & CELL BIOL, 3000 DR ROTTERDAM, NETHERLANDS
7. UNIV CALIF LOS ANGELES, SCH MED, DEPT PATHOL, LOS ANGELES, CA 90024 USA
8. UNIV LYON 1, LAB GENET JE382, F-69373 LYON 08, FRANCE
9. KYOTO UNIV, FAC MED, DEPT MOLEC ONCOL, KYOTO 608, JAPAN
10. HUMBOLDT UNIV BERLIN, FAK MED, INST HUMANGENET, O-1040 BERLIN, GERMANY
11. QUEENSLAND INST MED RES, HERSTON, QLD 4006 AUSTRALIA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Genetics & Heredity |
| IDS Number: UC637 |
| ISSN: 0964-6906 |
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