title: Biallelic BRCA2 mutations in two black South African children with Fanconi anaemia.
abstract: Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition, characterized cytogenetically by chromosomal instability and breakage secondary to impaired DNA repair mechanisms. Affected individuals typically manifest growth restriction and congenital physical abnormalities and most progress to hematological disease including bone marrow aplasia. A rare genetic subtype of FA (FA-D1) is caused by biallelic mutations in the BRCA2 gene. Affected individuals manifest severe congenital anomalies and significant pigmentary changes and are additionally at risk for early onset leukemia and certain solid organ malignancies, including Wilms tumors and brain tumors. Parents of affected individuals are obligate carriers for heterozygous BRCA2 mutations and are thus potentially at risk for adult onset cancers which fall within the hereditary breast and ovarian cancer spectrum. We present two cases of black South African patients with FA diagnosed with biallelic BRCA2 mutations and discuss the phenotypic consequences and implications for them and their families. Recognition of this severe end of the phenotypic spectrum of FA is critical in allowing for confirmation of the diagnosis as well as cascade screening and appropriate care of family members.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service & School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, Cnr Hospital & De Korte Street, Braamfontein, Johannesburg, 2000, South Africa. candice.feben@nhls.ac.za.
authors.forename: Candice
authors.identifier: 0000-0002-1296-3547
authors.initials: C
authors.lastname: Feben
authors.affiliation: Division of Human Genetics, National Health Laboratory Service & School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, Cnr Hospital & De Korte Street, Braamfontein, Johannesburg, 2000, South Africa.
authors.forename: Careni
authors.initials: C
authors.lastname: Spencer
authors.affiliation: Division of Human Genetics, National Health Laboratory Service & School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, Cnr Hospital & De Korte Street, Braamfontein, Johannesburg, 2000, South Africa.
authors.forename: Anneline
authors.initials: A
authors.lastname: Lochan
authors.affiliation: Division of Human Genetics & The Department of Medicine, The University of Cape Town, Cape Town, South Africa.
authors.forename: Nakita
authors.initials: N
authors.lastname: Laing
authors.affiliation: Division of Human Genetics & The Department of Medicine, The University of Cape Town, Cape Town, South Africa.
authors.forename: Karen
authors.initials: K
authors.lastname: Fieggen
authors.affiliation: Department of Human Genetics, Steve Biko Pretoria Academic Hospital & The University of Pretoria, Pretoria, South Africa.
authors.forename: Engela
authors.initials: E
authors.lastname: Honey
authors.affiliation: Faculty of Health Sciences, The University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Tasha
authors.initials: T
authors.lastname: Wainstein
authors.affiliation: Division of Human Genetics, National Health Laboratory Service & School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, Cnr Hospital & De Korte Street, Braamfontein, Johannesburg, 2000, South Africa.
authors.forename: Amanda
authors.initials: A
authors.lastname: Krause
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D013019:South Africa
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA2 mutations; Black South African patients; Cascade screening; Fanconi anaemia; Hereditary breast and ovarian cancer syndrome