title: Sequence variations in the Fanconi anaemia gene, FAC: pathogenicity of 1806insA and R548X and recognition of D195V as a polymorphic variant.
abstract: Fanconi anaemia (FA) is a rare autosomal recessive disorder associated with diverse clinical symptoms, increased chromosomal instability and a marked hypersensitivity to crosslinking agents. At least five complementation groups have been defined, the gene for group C (FAC) being the only FA gene cloned thus far. Several sequence variations have been detected in FA patients, whose assignment to group C, however, had not been ascertained by complementation studies. Using a functional assay, in which we tested the capacity of a variant sequence to correct the defect in FA-C lymphoblasts, we provide evidence for the pathogenic status of 1806insA and R548X and for non-pathogenicity of D195V.
authors.affiliation: Department of Human Genetics, Free University, Amsterdam, The Netherlands.
authors.forename: J R
authors.initials: JR
authors.lastname: Lo ten Foe
authors.forename: M T
authors.initials: MT
authors.lastname: Barel
authors.forename: P
authors.initials: P
authors.lastname: Thuss
authors.forename: M
authors.initials: M
authors.lastname: Digweed
authors.forename: F
authors.initials: F
authors.lastname: Arwert
authors.forename: H
authors.initials: H
authors.lastname: Joenje
mesh_terms: D018797:Cell Cycle Proteins; D018076:DNA, Complementary / Q000737:chemistry; D004268:DNA-Binding Proteins; D015245:Deoxyribonuclease BamHI / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D009154:Mutation; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016685:Mitomycin; D015245:Deoxyribonuclease BamHI; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific