title: Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia.
abstract: Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, The University of the Witwatersrand, Johannesburg, South Africa. Electronic address: candice.feben@nhls.ac.za.
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, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Wainwright
authors.affiliation: Department of Pediatrics, Universitas Hospital, The University of the Free State, Johannesburg, South Africa.
authors.forename: David
authors.initials: D
authors.lastname: Stones
authors.affiliation: Department of Pediatrics, Charlotte Maxeke Johannesburg Academic Hospital, 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; D015331:Cohort Studies; D005199:Fanconi Anemia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017384:Sequence Deletion; D013019:South Africa / Q000453:epidemiology
chemical_list: C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein
keywords: Black South African patients; Bone marrow aplasia; FANCG founder mutation; Fanconi anemia; Hematopoietic stem cell transplantation