title: Phenotypic consequences in black South African Fanconi anemia patients homozygous for a founder mutation.
abstract: OBJECTIVE
  Fanconi anemia is a genotypically and phenotypically heterogeneous condition, characterized microscopically by chromosomal instability and breakage. Affected individuals manifest growth restriction and congenital physical abnormalities; most progress to hematological disease including bone marrow aplasia. Black South African Fanconi anemia patients share a common causative founder mutation in the Fanconi G gene in 80% of cases (637_643delTACCGCC). The aim of this study was to investigate the genotype-physical phenotype correlation in a cohort of individuals homozygous for this mutation.
  
  
  METHODS
  Thirty-five black patients were recruited from tertiary level hematology/oncology clinics in South Africa. Participants were subjected to a comprehensive clinical examination, documenting growth, congenital anomalies, and phenotypic variability.
  
  
  RESULTS
  Descriptive statistical analysis showed significant growth abnormalities in many patients and a high frequency (97%) of skin pigmentary anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently (≥70%). Apart from malformations of the kidney (in 37%) and gastrointestinal tract (in 8.5%), congenital anomalies of other systems including the cardiovascular and central nervous systems, genitalia, and vertebrae were infrequent (<5%).
  
  
  CONCLUSIONS
  The diagnosis of Fanconi anemia in black South African patients before the onset of hematological symptoms remains a clinical challenge, with the physical phenotype unlikely to be recognized by those without dysmorphology expertise.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Candice
authors.initials: C
authors.lastname: Feben
authors.affiliation: Division of Human Genetics, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kromberg
authors.affiliation: Department of Pediatrics, Chris Hani Baragwanath Hospital and The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Wainwright
authors.affiliation: Department of Pediatrics, Universitas Hospital and The University of the Free State, Bloemfontein, South Africa.
authors.forename: David
authors.initials: D
authors.lastname: Stones
authors.affiliation: Department of Pediatrics, Polokwane/Mankweng Hospital Complex and The University of Limpopo, Limpopo, South Africa.
authors.forename: Chris
authors.initials: C
authors.lastname: Sutton
authors.affiliation: Department of Pediatrics, Charlotte Maxeke Johannesburg Academic Hospital and The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Janet
authors.initials: J
authors.lastname: Poole
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Tabitha
authors.initials: T
authors.lastname: Haw
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Amanda
authors.initials: A
authors.lastname: Krause
mesh_terms: D000293:Adolescent; D044383:Black People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004423:Ear / Q000002:abnormalities; D005124:Eye Abnormalities / Q000235:genetics; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000235:genetics*; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics*; D018703:Founder Effect; D041981:Gastrointestinal Tract / Q000002:abnormalities; D006228:Hand Deformities, Congenital; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D009154:Mutation; D010641:Phenotype; D012880:Skin Pigmentation / Q000235:genetics; D013019:South Africa
chemical_list: C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein