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Hereditary spastic paraplegia (HSP) comprises a large group of neurogenetic disorders characterized by progressive lower extremity spasticity. Neurological evaluation and genetic testing were completed in a Malian family with early-onset HSP. Three children with unaffected consanguineous parents presented with symptoms consistent with childhood-onset complicated HSP. Neurological evaluation found lower limb weakness, spasticity, dysarthria, seizures, and intellectual disability. Brain MRI showed corpus callosum thinning with cortical and spinal cord atrophy, and an EEG detected slow background in the index patient. Whole exome sequencing identified a homozygous missense variant in the adaptor protein (AP) complex 2 alpha-2 subunit (AP2A2) gene. Western blot analysis showed reduced levels of AP2A2 in patient-iPSC derived neuronal cells. Endocytosis of transferrin receptor (TfR) was decreased in patient-derived neurons. In addition, we observed increased axon initial segment length in patient-derived neurons. Xenopus tropicalis tadpoles with ap2a2 knockout showed cerebral edema and progressive seizures. Immunoprecipitation of the mutant human AP-2-appendage alpha-C construct showed defective binding to accessory proteins. We report AP2A2 as a novel genetic entity associated with HSP and provide functional data in patient-derived neuron cells and a frog model. These findings expand our understanding of the mechanism of HSP and improve the genetic diagnosis of this condition.

Introduction: According to the taxonomy of the International Association for the Study of Pain (IASP 2011), neuropathic pain (NeuP) is defined as “pain caused by a lesion or disease of the somatosensory nervous system”. NeuP is currently well-defined clinically, despite a high degree of etiological variation, and it has become a significant public health problem. This work aimed to study the situation regarding NeuP in current practice in Mali, as well as to analyze the therapeutic environment of the patients. Methodology: This was a retrospective and cross-sectional study, carried out in two phases: (1) compilation of the files of patients according to the ICD-11, over a period of 24 months (2) a second prospective phase regarding the Knowledge, Attitudes, and Practices (KAP) of general practitioners and neurologists in regard to NeuP. The focus of the first phase of the study was the files of the patients who had undergone a consultation at the Gabriel Touré UHC. The second phase of the study focused on the general practitioners (Community Health Centers (comHC) of Bamako) and neurologists (Malian or not). Results: Over the period of the study, 7840 patients were seen in consultation in the Department of Neurology, of whom 903 for NeuP, thus amounting to a NeuP frequency of 11.5%. Women accounted for 58.9% (532/903), with a sex ratio of 1.4. Using a comparative normal law, the difference in frequency was statistically significant between males and females (p

Migraine is a debilitating but benign disease that can affect the quality of life of patients, disrupt the emotional relationships and impact on educational and vocational activities. The aim of our work was to study the epidemiology and impact of migraine in schools in the urban district of GAO in Mali. This is a cross-sectional study among students in the city of Gao. The survey was conducted in 11 schools, each of which represented a cluster. The study involved 733 students and diagnosis of migraine was made according to the 2004 IHS criteria except the criterion for the number of crises. The overall prevalence of migraine in school was 17.3% (95% CI [14.6% to 20%]). The headache prevalence among students was 20% (95% CI [16.91% to 23.09]), it was significantly higher 23.0% in girls than in boys 14.8% (p