Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer. We report that a deletion mutation in the FANCG gene (c.637_643delTACCGCC) was present in 82% of FA patients in the black populations of Southern Africa. These patients originated from South Africa, Swaziland, Mozambique, and Malawi. The mutation was found on the same haplotype and was present in 1% of controls from the black South African population. These data indicate that the birth incidence of FA in this population is higher than 1 in 40 000, which is much higher than previously supposed, and suggest that the FANCG deletion is an ancient founder mutation in Bantu-speaking populations of sub-Saharan Africa.

Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

True hermaphroditism is defined by the presence of both testicular and ovarian tissue in an individual. True hermaphrodites usually present at birth with ambiguous genitalia, and subsequent invasive investigations are needed to confirm the diagnosis. Several large cohorts of black South Africans with true hermaphroditism have been described, and by far the majority of those investigated had a 46,XX karyotype, with absence of the SRY sequence. This paper represents the first report of the molecular investigation of mosiacism/chimerism as the cause of hermaphroditism in black southern African patients. It is the second report worldwide of a 46,XX/47,XY,+21 chimera, with the first described in a Japanese infant in 1994. Case 1 in the present study is a child who is a 46,XX/47,XY,+21 tetragametic chimera. Molecular studies revealed two paternal and two maternal alleles at four of ten STR loci investigated and three alleles at four of these loci. The young boy exhibited no features of Down syndrome, other than a unilateral single palmar crease. Cases 2 and 3 both have a 46,XX/46,XY karyotype. Chimerism is supported by molecular analysis in Case 2, and molecular studies were not done for Case 3.