Genetic disorders in the Indian community of South Africa

Objectives. To determine the range of genetic disorders in the Indian population of South Africa, assess relevant historical and demographic factors, and discuss the implications for medical and genetic care. Methods. WSW reviewed the archived data pertaining to patients seen in his paediatric practice in Durban during the past 45 years. Likewise, PB reviewed case details of persons encountered since 1972 in Cape Town, at outreach clinics, and in special institutions for the handicapped throughout South Africa. Additional information was accessed through the Cape Genetic Heritage archive. Results. In addition to the common ubiquitous worldwide genetic disorders, several rare heritable conditions are present in the Indian community of South Africa. These disorders are the consequence of the founder effect and reflect the biological heritage of the early immigrants. Demographic factors (notably endogamy) are also relevant in this respect. As a result of these processes, thalassaemia is by far the most common and important genetic disorder in the Indian population in the country. Conclusion. Awareness of the presence of specific genetic conditions in the Indian community of South Africa is important in the diagnostic process. In turn, diagnostic precision facilitates accurate prognostication and optimal medical and genetic management

Bone and Joint Disorders on Tristan da Cunha

In an investigation of bone and joint disorders among the islanders of Tristan da Cunha, a total of 111 individuals aged 35 years and over were examined. These represented 87% of the population in this age group. Serological studies of rheumatoid factor and radiographic examination of the hands were carried out respectively in 74% and 70010 of this adult population. The prevalence of rheumatoid arthritis and osteo-arthrosis did not differ to any great extent from that which would be expected to occur in a similar community in Europe. Classical gout was observed in one middle-aged male. Clinodactyly of the fifth finger was transmitted as an autosomal dominant trait in 12 members of the Glass family. Dupuytren's contracture, traumatic lesions and arthralgic complaints were frequently encountered.S. Afr. Med. J., 48, 743 (1974

X-Linked Deafness in a South African Kindred

The X-linked deafness of Nance is present in a South African kindred. Recognition of the familial pattern of the disorder, together with the characteristic clinical and audiometric features, permits diagnostic precision, thereby facilitating accurate genetic counselling and rational management. Linkage studies indicated that the loci for the Xg blood group and the deafness gene are unlikely to be very close to each other.S. Afr. Med. J., 48, 587 (1974)

X-linked deafness in a South African kindred

The X-linked deafness of Nance is present in a South African kindred. Recognition of the familial pattern of the disorder, together with the characteristic clinical and audiometric features, permits diagnostic precision, thereby facilitating accurate genetic counselling and rational management. Linkage studies indicated that the loci for the Xg blood group and the deafness gene are unlikely to be very close to each other.S. Afr. Med. J., 48, 587 (1974)

Digitotalar dysmorphism: Molecular elucidation

Dominantly inherited digitotalar dysmorphism (DTD), which is characterised by flexion contractures of digits and ‘rocker-bottom’ feet due to a vertical talus, was first described in a South African family of European stock in 1972. We review the clinical manifestations and document the molecular basis for DTD in this prototype family. This family was restudied in 1995 and 2006 and biological specimens were obtained for molecular studies. Since the distal arthrogryposes (DAs) are genetically heterogeneous, an unbiased approach to mutation identification was undertaken through whole-exome next-generation sequencing of DNA from a single DTD-affected female. Venous blood specimens were obtained for DNA banking and subsequent molecular studies. Analysis of the nine genes that had previously been shown to cause DAs revealed a pathogenic mutation in exon nine of TNNT3. The presence of the p.(Arg63His) missense mutation at position 63 of TNNT3 was confirmed through direct cycle sequencing of genomic DNA in six affected family members for whom DNA had been archived

Genetic mapping of retinitis pigmentosa implications for South African patients

No Abstract

Duchenne and Becker muscular dystrophy prevalence in South Africa and molecular findings in 128 persons affected

A genetic service for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) was initiated in Cape Town in 1987. Of the 143 DMD patients diagnosed during the period 1987-1992, 66 had a familial pattern of inheritance and 77 were apparently sporadic. Twenty BMD patients were identified, of whom 12 had other affected relatives and 8 were sporadic. Overall minimum prevalence rates of 1/100 000 for DMD and 1/55 000 for BMD were calculated. A markedly low DMD prevalence in the indigenous black population (1/250000) contributed tothe overall low DMD prevalence in South Africa when compared with that in the UK (1/40 000).By means of molecular methods, the diagnosis in 42% of the affected DMD males was confirmed by detection of deletions in the dystrophin gene. Deletions were identified in 50% of Indian, white and mixed ancestry patients. In contrast, only 22% of blacks had identifiable deletions.DMD appears to be underrepresented in the black population; the low deletion frequency in this group suggests that unique mutations not detectable by methods used in this study may be more frequent in these patients than in the other populations. The increased DMD frequency in Indians corroborates findings reported from the UK

A clinical and molecular investigation of two South African families with Simpson-Golabi-Behmel syndrome

Background. Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked recessive overgrowth syndrome manifesting primarily in boys and characterised by macrosomia, distinctive facial features and multiple congenital abnormalities. Although this rare condition is thought to be underdiagnosed, making a diagnosis is important as affected boys have a 7.5% risk of developing visceral tumours and surveillance is warranted. Mutations in GPC3 are found in up to 70% of boys affected with SGBS.Objectives. A clinical and molecular investigation of two boys with SGBS, probands B and S, and their mothers. Documentation of the clinical phenotype could assist with diagnosis in affected boys and will lead to early initiation of tumour surveillance.Methods. Hospital folders were reviewed and clinical consultations arranged for both probands and their mothers. Molecular investigations initially searched for whole-exon deletions in GPC3 followed by gene sequencing.Results. The clinical phenotype of both probands was consistent with that previously reported in the literature. The main features pointing towards the diagnosis were macrosomia, coarse facial features and macroglossia with a midline groove in the tongue. Proband B developed a Wilms tumour. He was found to have a novel mutation causing a premature stop codon.Conclusions. This research represents the first published report of SGBS in South Africa. Early recognition and confirmation of this condition is important in order to institute tumour surveillance and assist families with accurate recurrence risks

Transkei foot

An epidemiological investigation of bone and joint abnormalities in a Xhosa population revealed 6 females with a condition characterised by marked lateral deviation of the fifth toes. This disorder does not seem to have been previously described, and we therefore propose that it should be named 'Transkei foot'. The pathogenesis of the condition is obscure, but it is possible that it has a genetic basis.S. Afr. Med. J. 48, 961 (1974