The Utilization and Outcome of Diagnostic, Predictive, and Prenatal Genetic Testing for Huntington Disease in Johannesburg, South Africa

Sizer, Elaine B.; Haw, Tabitha; Wessels, Tina; Kromberg, J. G. R.; Krause, Amanda

doi:10.1089/gtmb.2011.0007

Cited by 18 publications

(22 citation statements)

References 13 publications

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“…This confirms the low uptake of prenatal testing for HD. 9,14,15 There is a North-South Choices after PND for Huntington disease H Bouchghoul et al decrease in PND uptake; the number of PND per couple in the Netherlands was higher than in more southern populations (2.8, 1-9 13 versus 1.6, 1-6). Interestingly, in our study the proportion of female and male carriers among those requesting PND was similar (50%), whereas in other studies more male carriers were found.…”

Section: Discussionmentioning

confidence: 99%

Prenatal testing in Huntington disease: after the test, choices recommence

et al. 2016

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The objective of this study was (1) to determine the impact of prenatal diagnosis (PND) for Huntington disease (HD) on subsequent reproductive choices and family structure; and (2) to assess whether children born after PND were informed of their genetic status. Out of 354 presymptomatic carriers of HD gene mutation, aged 18-45 years, 61 couples requested 101 PNDs. Fifty-four women, 29 female carriers and 25 spouses of male carriers, accepted to be interviewed (0.6-16.3 years after the last PND, median 6.5 years) on their obstetrical history and information given to children born after PND. Women were willing to undergo two or more PNDs with a final success rate of 75%. Reproductive decisions differed depending on the outcome of the first PND. If favourable, 62% couples decided against another pregnancy and 10% chose to have an untested child. If unfavourable, 83% decided for another pregnancy (P<0.01), and the majority (87%) re-entered the PND procedure. In contrast, after a second PND, only 37% asked for a PND and 30% chose to have an untested child. Thirty-three percent had both, tested and untested children. Among children born after PND, 10 years and older, 75% were informed of their genetic status. The decision to prevent transmission of the HD mutation is made anew with each pregnancy. Couples may need more psychological support after PND and pre-counselling sessions should take into account the effect of the outcome of a first PND on subsequent reproductive choices.

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Section: Discussionmentioning

confidence: 99%

Prenatal testing in Huntington disease: after the test, choices recommence

et al. 2016

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“…17 Several factors have continued to contribute to under-reporting of HD in this group including a lack of access to health-care services, a shorter average life-span, cultural beliefs that lead affected individuals to consult traditional healers rather than medical practioners and traditional medical training that HD is rare in black Africans. 27,28 The black South African families in the patient cohort were all from the Division of Human Genetics, NHLS/Wits in Johannesburg. It is noteworthy that there are no black South African HD families seen at the Division of Human Genetics, NHLS/UCT (unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Huntington disease in the South African population occurs on diverse and ethnically distinct genetic haplotypes

et al. 2013

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Huntington disease (HD) is a neurodegenerative disorder resulting from the expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene. Worldwide prevalence varies geographically with the highest figures reported in populations of European ancestry. HD in South Africa has been reported in Caucasian, black and mixed subpopulations, with similar estimated prevalence in the Caucasian and mixed groups and a lower estimate in the black subpopulation. Recent studies have associated specific HTT haplotypes with HD in distinct populations. Expanded HD alleles in Europe occur predominantly on haplogroup A (specifically high-risk variants A1/A2), whereas in East Asian populations, HD alleles are associated with haplogroup C. Whether specific HTT haplotypes associate with HD in black Africans and how these compare with haplotypes found in European and East Asian populations remains unknown. The current study genotyped the HTT region in unaffected individuals and HD patients from each of the South African subpopulations, and haplotypes were constructed. CAG repeat sizes were determined and phased to haplotype. Results indicate that HD alleles from Caucasian and mixed patients are predominantly associated with haplogroup A, signifying a similar European origin for HD. However, in black patients, HD occurs predominantly on haplogroup B, suggesting several distinct origins of the mutation in South Africa. The absence of high-risk variants (A1/A2) in the black subpopulation may also explain the reported low prevalence of HD. Identification of haplotypes associated with HD-expanded alleles is particularly relevant to the development of population-specific therapeutic targets for selective suppression of the expanded HTT transcript.

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“…[1992], Bloch et al [1992], Chapman [1992], Fox et al [1989] Canada (Vancouver) Discusses the psychological impact of predictive testing with an emphasis on description of protocol, unexpected results, increased risk, and legal and social aspects Adam et al [1993] Canada (Vancouver) Discusses prenatal testing using linked markers Simpson and Harding [1993] United Kingdom Discusses predictive testing on the brink of direct gene analysis Taylor [1994] Australia Review predictive testing requests prior to discovery of the HD gene Tolmie et al [1995] Scotland Reviews experiences with prenatal testing Whitefield et al [1996] New Zealand Reviews molecular diagnostic experiences in 100 patients Sanchez et al [1997] Spain Reviews diagnostic/predictive testing in 138 patients Mandich et al [1998] Italy Reviews experience at two centers Kromberg et al [1999] South Africa (Johannesburg) Australia (Victoria) Summarizes 10 years of experience with predictive and prenatal testing Futter et al [2009] South Africa (Capetown) Reviews predictive testing at one institution Dufrasne et al [2011] Montreal Reviews 15 years of experience with predictive testing Sizer et al [2012] South Africa Reviews uptake of predictive and prenatal testing; 9% of patients tested were positive for HDL2 Maciel et al [2013] South America Describes the lack of availability of genetic testing (25%) and counseling (66%) at 24 Huntington's disease (HD) centers Tanaka et al [2013] Japan Emphasizes barriers to genetic testing and counseling van Rij et al [2014a] Netherlands Reviews prenatal testing, 1998Arning et al [2015, Bernhardt et al [2009] Germany (Bochum) Focuses on gender differences in predictive testing decision making; reviews 10 years of predictive testing principles involved, and others focus more on the clinical outcomes (see Tables V and VI, respectively). Other ethical challenges for clinical practitioners include anonymous testing, counseling of patients and family members when an affected person learns he or she is unexpectedly homozygous (or, more likely, compound heterozygous) for an expanded CAG repeat, and counseling regarding expansions and contractions in and across the intermediate CAG repeat boundaries.…”

Section: Ethical Challengesmentioning

confidence: 99%

Genetic counseling and testing for Huntington's disease: A historical review

Nance

2016

American J of Med Genetics Pt B

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This manuscript describes the ways in which genetic counseling has evolved since John Pearson and Sheldon Reed first promoted "a genetic education" in the 1950s as a voluntary, non-directive clinical tool for permitting individual decision making. It reviews how the emergence of Huntington's disease (HD) registries and patient support organizations, genetic testing, and the discovery of a disease-causing CAG repeat expansion changed the contours of genetic counseling for families with HD. It also reviews the guidelines, outcomes, ethical and laboratory challenges, and uptake of predictive, prenatal, and preimplantation testing, and it casts a vision for how clinicians can better make use of genetic counseling to reach a broader pool of families that may be affected by HD and to ensure that genetic counseling is associated with the best levels of care.

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The Utilization and Outcome of Diagnostic, Predictive, and Prenatal Genetic Testing for Huntington Disease in Johannesburg, South Africa

Cited by 18 publications

References 13 publications

Prenatal testing in Huntington disease: after the test, choices recommence

Prenatal testing in Huntington disease: after the test, choices recommence

Huntington disease in the South African population occurs on diverse and ethnically distinct genetic haplotypes

Genetic counseling and testing for Huntington's disease: A historical review

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