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| Association of complementation group and mutation type with clinical outcome in Fanconi anemia |
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| Author(s): Faivre L, Guardiola P, Lewis C, Dokal I, Ebell W, Zatterale Z, Altay C, Poole J, Stones D, Kwee ML, van Weel-Sipman M, Havenga C, Morgan N, de Winter J, Digweed M, Savoia A, Pronk J, de Ravel T, Jansen S, Joenje H, Gluckman E, Mathew CG |
| Source: BLOOD Volume: 96 Issue: 13 Pages: 4064-4070 Published: DEC 15 2000 |
| Times Cited: 76 References: 44 |
| Abstract: Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (C) 2000 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mathew, CG (reprint author), Guys Hosp, GKT Sch Med, Div Mol & Med Genet, 8th Floor,Guys Tower, London SE1 9RT, England |
Addresses:
1. Guys Hosp, GKT Sch Med, Div Mol & Med Genet, London SE1 9RT, England
2. Hop St Louis, Dept Hematol, Bone Marrow Transplant Unit, Paris, France
3. Hammersmith Hosp, Dept Hematol, London, England
4. Free Univ Berlin, Klinikum Rudolf Virchow, D-1000 Berlin, Germany
5. Osped Elena Aosta, Naples, Italy
6. Hacettepe Univ, Ankara, Turkey
7. Baragwanath Hosp, Bertsham, South Africa
8. Univ Orange Free State, Sch Med, Dept Human Genet, Bloemfontein, South Africa
9. Univ Orange Free State, Sch Med, Dept Paediat, Bloemfontein, South Africa
10. Free Univ Amsterdam, Dept Human Genet, Amsterdam, Netherlands
11. Leiden Univ, Med Ctr, Dept Pediat, NL-2300 RA Leiden, Netherlands
12. IRCCS, Osped CSS, Genet Serv, San Giovanni Rotondo, Italy
13. Univ Witwatersrand, Dept Human Genet, Johannesburg, South Africa |
| Publisher: AMER SOC HEMATOLOGY, 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA |
| Subject Category: Hematology |
| IDS Number: 380PD |
| ISSN: 0006-4971 |
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