title: Classification of Fanconi anemia patients by complementation analysis: evidence for a fifth genetic subtype.
abstract: Fanconi anemia (FA) is an autosomal recessive disease with diverse clinical symptoms, life-threatening progressive panmyelopathy, and cellular hypersensitivity to cross-linking agents. Currently, 4 genetic subtypes or complementation groups (FA-A through FA-D) have been distinguished among 7 unrelated FA patients. We report the use of genetically marked FA lymphoblastoid cell lines representing each of the 4 presently known complementation groups to classify 13 unrelated FA patients through cell fusion and complementation analysis. Twelve cell lines failed to complement cross-linker sensitivity in fusion hybrids with only 1 of the 4 reference cell lines and could thus be unambiguously classified as FA-A (7 patients), FA-C (4 patients), or FA-D (1 patient). One cell line complemented all 4 reference cell lines and therefore represents a new complementation group, designated FA-E. These results imply that at least 5 genes appear to be involved in a pathway that, when defective, causes bone marrow failure in FA patients.
authors.affiliation: Department of Human Genetics, Free University, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Joenje
authors.forename: J R
authors.initials: JR
authors.lastname: Lo ten Foe
authors.forename: A B
authors.initials: AB
authors.lastname: Oostra
authors.forename: C G
authors.initials: CG
authors.lastname: van Berkel
authors.forename: M A
authors.initials: MA
authors.lastname: Rooimans
authors.forename: T
authors.initials: T
authors.lastname: Schroeder-Kurth
authors.forename: R D
authors.initials: RD
authors.lastname: Wegner
authors.forename: J J
authors.initials: JJ
authors.lastname: Gille
authors.forename: M
authors.initials: M
authors.lastname: Buchwald
authors.forename: F
authors.initials: F
authors.lastname: Arwert
mesh_terms: D002459:Cell Fusion; D002460:Cell Line; D002869:Chromosome Aberrations; D005199:Fanconi Anemia / Q000145:classification* / Q000235:genetics / Q000473:pathology; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male