Association of complementation group and mutation type with clinical outcome in Fanconi anemia

Laurence Faivre, Philippe Guardiola, Cathryn Lewis, Inderjeet Dokal, Wolfram Ebell, Ariana Zatterale, Cigdem Altay, Janet Poole, David Stones, Mei Lan Kwee, Margreet Van Weel-Sipman, Charmaine Havenga, Neil Morgan, Johan De Winter, Martin Digweed, Anna Savoia, Jan Pronk, Thomas De Ravel, Stander Jansen, Hans JoenjeEliane Gluckman, Christopher G. Mathew

Research output: Contribution to journalArticlepeer-review


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 1VS4 + 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.

Original languageEnglish
Pages (from-to)4064-4070
Number of pages7
Issue number13
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hematology

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