Complementation analysis in Fanconi anemia: Assignment of the reference FA-H patient to group A

Fanconi anemia (FA) is an autosomal recessive disorder with diverse clinica l symptoms and extensive genetic heterogeneity. Of eight FA genes that have been implicated on the basis of complementation studies, four have been id entified and two have been mapped to different loci; the status of the gene s supposed to be defective in groups B and H is uncertain. Here we present evidence indicating that the patient who has been the sole representative o f the eighth complementation group (FA-H) in fact belongs to group FA-A. Pr evious exclusion from group A was apparently based on phenotypic reversion to wild-type rather than on genuine complementation in fusion hybrids. To a void the pitfall of reversion, future assignment of patients with FA to new complementation groups should conform with more-stringent criteria. A new group should be based on at least two patients with FA whose cell lines are excluded from all known groups and that fail to complement each other in f usion hybrids, or, if only one such cell line were available, on a new comp lementing gene that carries pathogenic mutations in this cell line. On the basis of these criteria, the current number of complementation groups in FA is seven.