title: Novel mutations and polymorphisms in the Fanconi anemia group C gene.
abstract: Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.
authors.affiliation: Division of Medical and Molecular Genetics UMDS, Guy's Hospital, London, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Gibson
authors.forename: N V
authors.initials: NV
authors.lastname: Morgan
authors.forename: L H
authors.initials: LH
authors.lastname: Goldstein
authors.forename: I C
authors.initials: IC
authors.lastname: Pearson
authors.forename: I P
authors.initials: IP
authors.lastname: Kesterton
authors.forename: N J
authors.initials: NJ
authors.lastname: Foot
authors.forename: S
authors.initials: S
authors.lastname: Jansen
authors.forename: C
authors.initials: C
authors.lastname: Havenga
authors.forename: T
authors.initials: T
authors.lastname: Pearson
authors.forename: T J
authors.initials: TJ
authors.lastname: de Ravel
authors.forename: R J
authors.initials: RJ
authors.lastname: Cohn
authors.forename: I M
authors.initials: IM
authors.lastname: Marques
authors.forename: I
authors.initials: I
authors.lastname: Dokal
authors.forename: I
authors.initials: I
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Marsh
authors.forename: S
authors.initials: S
authors.lastname: Ball
authors.forename: R D
authors.initials: RD
authors.lastname: Milner
authors.forename: J C
authors.initials: JC
authors.lastname: Llerena
authors.forename: E
authors.initials: E
authors.lastname: Samochatova
authors.forename: S P
authors.initials: SP
authors.lastname: Mohan
authors.forename: P
authors.initials: P
authors.lastname: Vasudevan
authors.forename: F
authors.initials: F
authors.lastname: Birjandi
authors.forename: A
authors.initials: A
authors.lastname: Hajianpour
authors.forename: M
authors.initials: M
authors.lastname: Murer-Orlando
authors.forename: C G
authors.initials: CG
authors.lastname: Mathew
mesh_terms: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; 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