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Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries.

Hemophilia A and B are X-linked recessive inherited bleeding disorders that have a profound impact on the family of affected individuals. Education is vital to enable women to appreciate the implications of being a carrier and the implications for a prospective child. Prior research has shown that cultural, socio-economic and linguistic issues in South Africa are major barriers to communication for first-language Xhosa-speakers. This exploratory study aimed to investigate the basic knowledge of genetic inheritance among this cultural group in order to promote culturally-sensitive, effective genetic counseling. Ten in-depth interviews were conducted with Xhosa-speaking mothers or caregivers of boys with hemophilia. Results suggest that the participants had a very limited understanding of the clinical management, genetic consequences and cause of hemophilia. While treatment and care by health care service providers was fully accepted, several participants believed that traditional methods would provide them with more satisfactory explanations. These findings suggest that there is a critical need for socio-culturally tailored, language-specific education for families with hemophilia.

Linkage analysis has been performed on a large South African family of British origin in which 39 persons in 6 generations had early onset Type I autosomal dominant retinitis pigmentosa (ADRP). Tight linkage was excluded between the disease and the D3S47 locus on chromosome 3. This finding is further evidence for genetic heterogeneity in ADRP.

Analysis of exon ORF15 of the RPGR gene has revealed a novel mutation in a South African family with X-linked retinitis pigmentosa (XLRP), which has implications for the rest of the family in terms of pre-symptomatic testing. The ability to test for this mutation will be beneficial for the accurate determination of carrier status in female relatives who may have been unaware of their risk before this study was performed. This work also highlights the need to be aware of the ramifications of mutation testing in what may appear to be small families. This is the first report of an RPGR ORF15 mutation in a South African family of mixed ancestry.

Purpose Technology for quantitative measurement of fundus autofluorescence (AF). Methods Scanning laser ophthalmoscopes (SLO’s, HRA2 and Spectralis, Heidelberg Eng.) were modified by insertion of an internal AF reference to account for variable laser power and detector sensitivity. 30° images (mean of 9 without histogram stretching) were acquired from normal test subjects (10-60 y/o) after a 20 s bleaching period,.. Quantified AF (qAF) was calculated from the reference gray level (GL), the zero GL, the media and the magnification (refractive error). The linearity of the system, field uniformity, effect of refractive error, and reproducibility were tested. qAF measurements were then done on 22 patients with Stargardt disease (STGD ) and 11 patients with retinitis pigmentosa (RP). Results The linear detection range extended to 175 GL. Field uniformity was better than 5% in a central 20°-diameter circle. The recorded AF and the square of the image magnification were inversely related. Different day reproducibility was 4.1 % at the fovea. Median inter-instrument reproducibility (Spectralis and the HRA2) was 7.4 %. Normals. qAF highly correlated with age (central qAF = 8.8+3.5*Age, p