Clinical, paraclinical and genetic aspects of autosomal recessive cerebellar ataxias (ARCA) in Mali.

Introduction: Autosomal recessive cerebellar ataxias (ARCA) are a group of rare and heterogynous neurodegenerative diseases mainly characterized by unbalance and walking difficulty and movement incoordination. Objectives: To clinically and paraclinically characterize ARCA in the department of Neurology at the Teaching Hospital of Point G and identify the underlying genetic defect. Patients and method: We have conducted a longitudinal and prospective study from January 2018 to December 2020. Patients with ARCA phenotype seen in the Department of Neurology at the Teaching Hospital of Point "G" were enrolled. Results: We have enrolled 7 families totaling 13 patients after giving an informed verbal and written consent. The sex ratio was 2.2 in favor of males, Kayes region and Fulani ethnic group were respectively the most represented region and ethnic group.Walking difficulty represented the major symptom followed by loss of vibration and joint sense, nystagmus, dysarthria and skeletal deformities. Alpha-foetoprotein level was high in one patient. Genetic testing confirmed Friedreich ataxia in one family and was not conclusive in 4 families. Conclusion: This study showed that ARCA are not uncommon in Mali and genetic testing is crucial to confirm the diagnosis.

Introduction: Les ataxies cérébelleuses autosomiques récessives (ACAR) constituent un groupe de maladies neurodégénératives rares et hétérogènes caractérisées essentiellement par un trouble de l'équilibre et de la marche, et un trouble de la coordination des mouvements. Objectifs: Caractériser les signes cliniques, paracliniques et génétiques des ataxies cérébelleuses autosomiques récessives au Service de Neurologie du CHU du Point "G". Patients et méthodes: Nous avons réalisé une étude de cas enrôlé dans le cadre d'une étude longitudinale et prospective allant de Janvier 2018 à Décembre 2020, portant sur des patients présentant des symptômes d'ACAR et ayant donné leur consentement éclairé. Résultats: Nous avons enrôlé sept familles totalisant 13 patients. Le sexe ratio était de 2,2 en faveur des hommes, la région de Kayes était la plus représentée et l'ethnie peulh était majoritaire. Les troubles de la marche ont représenté les signes majeurs suivis de troubles de la sensibilité profonde, de nystagmus, de dysarthrie, et des déformations ostéoarticulaires. L'alpha-foetoprotéine était élevée chez une patiente. Le test génétique a retrouvé l'ataxie de Friedreich dans une famille et n'a pas été concluant dans quatre autres. Conclusion: Cette étude montre que les ACAR ne sont pas rares au Mali et l'exploration génétique constitue un outil indispensable pour leur diagnostic de certitude.

Diagnostic et évaluation de la réponse thérapeutique de la leucémie myéloïde chronique au Mali par l'hybridation in situ fluorescente / Diagnosis and evaluation of the response to treatment of chronic myeloid leukaemia in Mali by fluorescent in situ hybridization

La leucémie myéloïde chronique (LMC) est une hémopathie maligne caractérisée par la présence du chromosome Philadelphie ou du gène de fusion BCR/ABL1. Au Mali, les approches génétiques de diagnostic et d'évaluation de la réponse thérapeutique de la LMC font défaut d'où l'intérêt de développer la méthode FISH (Hybridation in situ en Fluorescence) pour diagnostiquer et évaluer la réponse thérapeutique de la LMC. Méthodes. Nous avons analysé les cellules sanguines de 25 patients référés pour diagnostic ou évaluation thérapeutique de la LMC. Nous avons réalisé la FISH sur des cellules interphasiques et des métaphases, et la capture d'images cellulaires a été faite avec un microscope à épifluorescence. Résultats. Au total, 25 patients ont été inclus dont 16 pour diagnostic et 9 pour évaluation thérapeutique. Nous avons obtenu un taux de succès de 92% pour l'obtention des métaphases. En outre, nous avons observé des réarrangements ABL1/BCR à la FISH chez 22 des 25 patients. Parmi ces 22 patients, 16 ont présenté un patron de signaux typiques et 6 des patrons de signaux atypiques. Conclusion. Nous avons établi la technique FISH au Mali pour le diagnostic et l'évaluation thérapeutique de la LMC et identifié des formes atypiques de la translocation t(9 ;22).

Objective. Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the presence of the Philadelphia chromosome or its molecular equivalent, the BCR/ABL1 fusion gene. Diagnosis and monitoring of CML are done by detecting this chromosome, the BCR/ABL1 gene, or the BCR/ABL1 transcript. In Mali, genetic tools of diagnosis and follow-up are still lacking, so we did this study with the objectives of developing the FISH technique to diagnose, to follow up, and to characterize the cytogenetic profile of CML patients. Methods. We carried out FISH technique by using the dual color dual fusion probe for BCR/ABL1 on interphase nuclei and metaphases. Slides were scanned with an epifluorescence microscope. Results. A total of 25 patients (16 for diagnostic and 9 for follow-up) were included. We achieved a 92% success rate for obtaining metaphases. The BCR/ABL1 gene fusion signal was present in 22 patients. Among those 22 patients, 16 presented a typical signal pattern and 6 presented atypical signal patterns. Conclusion. We set up the FISH technique in Mali for the diagnosis and the follow-up of CML patients and identified atypical translocation of t(9;22).

[Clinical and laboratory features of recessive Limb Girdle Muscular dystrophies in the Department Neurology of University Hospital of Point G]. / Aspects Cliniques et Paracliniques des Myopathies des Ceintures Récessives au Service de Neurologie du CHU Point G.

INTRODUCTION: Limb-Girdle Muscular dystrophies (LGMD) is a group of inherited diseases characterized by predominantly proximal and limb muscle weakness. These are rare diseases that have not been well studied in sub-saharan Africa. The aim of our was the clinical and paraclinical characterization of patients with recessive LGMD at the Department of Neurology of the Teaching Hospital of Point G. PATIENTS AND METHODS: We conducted a longitudinal prospective study which took place from March 2014 to May 2019. Patients with recessive LGMD phenotype were enrolled. Sociodemographic, clinical and laboratory data were analyzed. RESULTS: We enrolled 46 families (67 patients), i.e. a frequency of 16.7% among the neurodegenerative diseases seen in the service. Among them, 45.6% came from the Sikasso region. Autosomal recessive inheritance pattern was suspected in 67.4% of the families. Symptoms appeared mainly in the first decade of life. Proximal muscle weakness was found in almost all patients. Cardiac examination showed dilated cardiomyopathy in 4.5% of cases. CONCLUSION: Limb-Girdle muscular dystrophy is a disabling disease that is found in Mali. Further study of these cases could elucidate the underlying genetic defects.

Blastic plasmacytoid dendritic cell leukemia in a black malian.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy, that most commonly manifests as cutaneous lesions. A 19-year-old Malian female was admitted to the Unit of Medicine of Hopital du Mali with anemia, fever, weakness, and weight loss. On physical examination she was wasted, pale, febrile (37.4°C), and had inguinal and axillary lymphadenopathies. The complete blood count found pancytopenia with Hemoglobin level of 4.8 g/dL, Leucocytes count of 1900/µL (neutrophil: 300/µL), and platelets count of 56 000/µL. The ultrasonographic examination found hepatomegaly and splenomegaly. The bone marrow biopsy and flow cytometer analysis were in keeping with a diagnosis of BPDCN. The patient, unfortunately, was lost four months later after her hospital admission due to late diagnosis by septicemia. The early diagnosis and availability of specific drugs for acute leukemia could improve the clinical outcome of patients with BPDCN in Mali.

Polymorphism in a human chromosome-specific interstitial telomere-like sequence at 22q11.2.

Interstitial telomeric sequences (ITSs) are common in human. We previously reported the presence of an ITS at 22q11.2 which is in the vicinity of the genomically unstable region involved in 22q11 rearrangements. Recently, we studied the molecular status of the ITS 22q11.2 in the normal population. The amplification of an ITS at 22q11.2 showed different patterns ranging from 1-4 kb, confirming the highly polymorphic nature of this sequence. The linkage analysis of the ITS at 22q11.2 in members of 10 different families demonstrated a strong relation between offspring and parents. In contrast, the study of a DiGeorge case and his 2 parents revealed the presence of a novel allele probably inherited from the father. These results open an avenue for the use of this sequence as an allelic marker, and its implication in 22q11.2-related pathogenesis.

Identification of a human chromosome-specific interstitial telomere-like sequence (ITS) at 22q11.2 using double-strand PRINS.

Interstitial telomeric sequences (ITSs), telomere-like repeats at intrachromosomal sites, are common in mammals and consist of tandem repeats of the canonical telomeric repeat, TTAGGG, or a repeat similar to this. We report that the ITS in human chromosome region 22q11.2 is, in the sequenced genome database, 101 tandem repeats of the sequence TTAGGGAGG. Using the primed in situ labeling (PRINS) technique and primers against the canonical telomeric repeat (TTAGGG), we illuminated telomeric sites for all chromosomes and an ITS locus at 22q11.2. Using the TTAGGGAGG sequence, we designed PRINS primers that efficiently and specifically illuminate the 22q11.2 ITS locus without illuminating telomeric and other ITS loci. The 22q11.2 locus has more repeat units than other ITSs loci enabling an unprecedented high detection frequency for this interstitial telomere locus. The 22q11.2 is associated with hot spots for disease-related chromosome breaks for multiple disorders, such as DiGeorge syndrome and chronic myeloid leukemia. We describe our findings that the ITS at 22q11.2 is in the same area of, and proximal to the common rearrangement region of multiple disorders. We suggest that the ITS might be involved in DNA repair processes in this area to protect the chromosome from more serious damage.