Clinical and Genetic Aspects of Huntington’s Disease in the Malian Population

Abstract

Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by mutation in the HTT gene and characterized by involuntary movements as well as cognitive and behavioral impairment. Since its first description 150 years ago, studies have been reported worldwide. However, genetically confirmed cases have been scarce in Africa. Objective: To describe the clinical and genetic aspects of HD in the Malian population. Methods: Patients with HD phenotype and their relatives were enrolled after obtaining consent. Symptoms were assessed using the Total Motor Scale (TMS) of the United Huntington’s Disease Rating Scale (UHDRS) and the Mini-Mental State Examination (MMSE). Brain imaging and blood tests were performed to exclude other causes. DNA was extracted for HTT sequencing. Results: Eighteen patients (13 families) with a HD phenotype were evaluated. A familial history of the disease was found in 84.6% with 55.5% of maternal transmission. The average length of the HTT CAG repeat was 43.6±11.5 (39–56) CAGs. The mean age at onset was 43.1±9.7years. Choreic movements were the predominant symptoms (100% of the cases) with an average TMS of 49.4±30.8, followed by cognitive impairment (average MMSE score: 23.0±12.0) and psychiatric symptoms with 22.2% and 44.4%, respectively. Conclusion: This is one of the largest HD cohorts reported in Africa. Increasing access to genetic testing could uncover many other HD cases and disease-modifying genetic variants. Future haplotype and psychosocial studies may inform the origin of the Malian mutation and the impact of the disease on patients and their relatives.

An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different tribes in 6 sub-Saharan African countries

“…The mHTT tract sizes in our patients and their asymptomatic relatives were similar to the previously reported sizes in both black South Africans 27,33 and in HD cases in other ethnic groups 25 , however, several observations from our study -and in line with previous studies -suggest that the HTT locus in indigenous sub-Saharan African populations is possibly more stable than in Europeans 35 . Firstly, the commonest CAG repeat size in our cohort was 15, similar to previous reports in black south Africans which is less than the average tract sizes in Europeans (18) and Asians (17) 36,37 . Secondly, all HD cases in our study had CAG tracts within the full penetrance range (>39 repeats), comparable to reports from black south Africans where 98-99% of black patients with HD had repeats sizes within full penetrance range 27,33 .…”

“…Elsewhere in Africa, clinical accounts of HD have been reported from Nigeria, Senegal, South Africa, Sudan, Tanzania, Togo, Uganda and Zimbabwe [11][12][13][14][15][16][17] . Genetic testing was used in the reporting of cases positive for Huntingtin mutation (mHTT) in Burkina Faso, South Africa, Egypt, Morocco, Mali and the Gambia [18][19][20][21][22][23] . However, the knowledge about the exact origin and the distribution of mHTT in the continent is sparse.…”

The First Case of Huntington’s Disease like 2 in Mali, West Africa

“…To our knowledge, this is the first family with HDL2 reported on the African continent outside southern Africa. The family described here is from Timbuktu where 33.3% of our previously reported HD cases originated [12]. Moreover, the family has a Songhai ethnic background, a Bantu-speaking ethnic group that probably originated from the hypothetic Bantu expansion across sub-Saharan Africa as did many of the people in South Africa, suggesting a possible common founder [13].…”