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Novel mutations and polymorphisms in the Fanconi anemia group C gene
Author(s) -
Gibson Rachel A.,
Morgan Neil V.,
Goldstein Laura H.,
Pearson Ian C.,
Kesterton Ian P.,
Foot Nicola J.,
Jansen Stander,
Havenga Charmaine,
Pearson Thomas,
de Ravel Thomy J.,
Cohn Richard J.,
Marques Isabel M.,
Dokal Inderjeet,
Roberts Irene,
Marsh Judith,
Ball Sarah,
Milner R. David,
Llerena Juan C.,
Samochatova Elena,
Mohan Sheila P.,
Vasudevan Pushpa,
Birjandi Farkondeh,
Hajianpour Atieh,
MurerOrlando Manuela,
Mathew Christopher G.
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)8:2<140::aid-humu6>3.0.co;2-f
Subject(s) - biology , fanconi anemia , genetics , complementation , gene , restriction fragment length polymorphism , single strand conformation polymorphism , mutation , microbiology and biotechnology , genotype , mutant , dna repair
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, 1312V, 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 homozygous 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. © 1996 Wiley‐Liss, Inc.