title: Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation.
abstract: BACKGROUND
  Fanconi anaemia (FA) is an autosomal recessive, genetically heterogeneous disorder, characterised by interstrand crosslink-induced chromosome breaks, congenital abnormalities and predisposition to malignancies. It has a prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in the FANCG gene occurs in the homozygous state in 77.5% of southern African blacks.
  
  
  OBJECTIVE
  To locate additional pathogenic mutations in the FANCG gene of black FA patients who were heterozygous for the founder mutation. Methods. Further mutation analysis of the FANCG gene was undertaken in 7 patients clinically suspected of having FA. The parents of two of the patients were tested for the presence of the founder mutation to determine true heterozygosity in the patients. To clarify whether or not previously unreported variants were pathogenic, 58 random black SA individuals were screened.
  
  
  RESULTS
  Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was found to have a single base substitution resulting in a splice site mutation (c.1636+1G>A). The remaining three patients were not found to harbour any pathogenic mutations. Two non-pathogenic variants were also identified among the seven patients.
  
  
  CONCLUSIONS
  The results of this small sample suggest that a second common mutation in the FANCG gene is unlikely in this population. However, FANCG sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis.
authors.affiliation: Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. tasha.wainstein@nhls.ac.za.
authors.forename: Tasha
authors.initials: T
authors.lastname: Wainstein
authors.forename: Robyn
authors.initials: R
authors.lastname: Kerr
authors.forename: Claire L
authors.initials: CL
authors.lastname: Mitchell
authors.forename: Smita
authors.initials: S
authors.lastname: Madaree
authors.forename: Fahmida B
authors.initials: FB
authors.lastname: Essop
authors.forename: Elana
authors.initials: E
authors.lastname: Vorster
authors.forename: Rosalind
authors.initials: R
authors.lastname: Wainwright
authors.forename: Janet
authors.initials: J
authors.lastname: Poole
authors.forename: Amanda
authors.initials: A
authors.lastname: Krause
mesh_terms: D044383:Black People; D004252:DNA Mutational Analysis; D005199:Fanconi Anemia / Q000235:genetics*; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics*; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D013019:South Africa
chemical_list: C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein