An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa

Background: Africans are underrepresented in Huntington\u27s disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent; however, recent work has shown the existence of a unique Htt haplotype in South-Africa specific to indigenous Africans. Objective: We aimed to investigate the CAG trinucleotide repeats expansion in the Htt gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa. Methods: We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the mHtt gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region. Results: HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the mHTT; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the mHTT; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD-bar three who were juvenile onset of \u3c21 years-were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54-16 kya ago: Nilo-Sahara and Niger-Congo. Conclusion: This is the first study examining HD in multiple sites in sub-Saharan Africa. We demonstrated that HD is found in multiple ethnic groups residing in five sub-Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio-economic impact, and genetic origins need further exploration and reappraisal

Current clinical presentations of AIDS dementia in a tropical environment: study of 26 observations in the neurology department of the University Hospital of Conakry

Abstract Introduction In sub-Saharan Africa (SSA), the clinical and progressive diagnostic certainty of AIDS dementia is difficult to establish due to under-medicalization and delays in consultation and especially the diversity of etiologies of demented states. Material and methods We carried out a retrospective study of 196 patients hospitalized for dementia syndrome between 2016 and 2021 in the neurology department of the University Hospital of Conakry. The criteria labeled in this study are those retained by the DSM-IV and the classification of the American Academy of Neurology (AAN) developed in accordance with the WHO. Results HIV etiology was identified in patients aged 44–67 years (17 women and 19 men). The clinical picture was dominated by severe cognitive disorders, slowed ideation, memory disorders and reduced motor skills associated with personality changes. Neurological examination revealed dysphoric disorders in most patients, sphincter abnormalities in 13 cases and labio-lingual tremor in 11 cases. Diagnosis was based on positive serological tests for HIV1 antibodies (25 cases) and HIV2 antibodies (1 case) using the Elisa and Western blot techniques, and the presence of discretely hypercellular CSF. Magnetic resonance imaging contributed to the diagnosis, showing diffuse white matter abnormalities with hyper signals on T2-weighted or FLAIR sequences. Conclusion This study shows a non-stereotype clinical picture of AIDS dementia requiring a differential diagnosis with other infectious dementias. These results are important for the therapeutic and prognostic discussion