Souleymane Coulibaly

Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malins ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population.

Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19

We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43.

Genetic testing and counseling for hereditary neurological diseases in Mali

As genetic advances become incorporated into health care delivery, disparities between developing and developed countries may become greater. By addressing genetic health care needs and specific differences of developing countries, these disparities may be mitigated. We sought to describe the attitudes and knowledge of subjects with hereditary neurological diseases in Mali before and after receiving genetic testing and counseling for the first time. A questionnaire of attitudes and knowledge items was adapted and piloted for use in Mali. We found that the majority of subjects had positive attitudes toward genetic testing and counseling, both before and afterwards. Subjects responded to approximately half of the knowledge questions regarding hereditary transmission correctly before and after genetic testing and counseling. Neither overall attitudes nor knowledge scores changed significantly from baseline. Concerns about confidentiality were expressed by the majority of subjects. These findings indicate that, despite limited knowledge of patterns of inheritance, Malians understood the sensitive nature of this information and were favorable toward receiving genetic testing and counseling for diagnostic and prognostic purposes.

Novel mutation in the ATM gene in a Malian family with ataxia telangiectasia

Dear Sirs, Ataxia telangiectasia (A-T) is a rare, autosomal recessive disorder of childhood characterized by progressive cerebellar ataxia, telangiectasia, and immune defects, and is caused by mutations in the ataxia-telangiectasia mutated (ATM) gene [1]. The incidence of the disease is about 1 in 40,000 to 100,000 births [2]. A-T has been reported worldwide [3], but reports of this disease in Africa are rare and generally limited to clinical description. We describe a Malian family with parental consanguinity (Fig. 1a) and three of ten children presenting with cerebellar symptoms in early childhood. Two patients, 14- and 10-year-old boys, had normal births and development until age 2, when they presented with progressive gait difficulty, including difficulty stopping when running and falls. They both later developed slurred speech, weakness, and decreased coordination of the upper extremities. No sensory or bladder difficulty was noted. Family history was remarkable for a grandfather who died at age 75 and had balance problems since he was a teenager. Fig. 1 Pedigree and genetic features of the family. a Pedigree of the family showing consanguinity, and unaffected (white) and affected (black) individuals. b Sequencing shows a homozygous T7985A mutation (asterisk) in ATM. c ATM protein alignment in various ... Neurological examination of both patients showed an ataxic gait, markedly reduced hand coordination, and nystagmus on fixation and lateral gaze. They had slight distal weakness and atrophy in the lower legs. Reflexes were normal to reduced, and the Babinski sign was absent. The older brother had scoliosis. Cardiologic examination and testing were normal. Brain CT scan showed cerebellar atrophy with prominent cisterna magna. Vitamin E and beta and gamma tocopherol serum levels were normal. Genetic testing for Friedreichs ataxia was negative. A follow-up clinical assessment showed oculomotor apraxia, ocular telangiectasia, and square wave jerks. The parents noted that the patients had recurrent diarrhea and upper respiratory infections. These new findings were in favor of ataxia telangiectasia (Table 1). Additional blood testing showed high alphafetoprotein (AFP) levels and low IgA, IgE, and IgG2 levels. Also, aspartate and alanine aminotransferases (AST, ALT), and C-reactive protein (CRP) were elevated in the two patients, suggesting liver dysfunction. Genetic analysis of the ATM gene identified a novel homozygous single-nucleotide substitution at position c.7985T > A (Fig. 1b), predicting the amino acid substitution V2662D. Five available unaffected siblings did not have this sequence variant. The V2662 residue lies in a predicted ATP binding domain [3] and is conserved across a broad range of vertebrate species (Fig. 1c). In addition, this non-conservative amino acid change yields a score of –3 according to the BLOSUM 62 substitution matrix [4], and was not found in 100 ethnically matched controls, suggesting that the mutation found here is likely deleterious. Table 1 Summary of clinical and laboratory findings in patients More recently, the parents noticed that their 2-year-old son also had an ataxic gait. His AFP levels were elevated, but he had no telangiectasias. This highlights the usefulness of AFP testing in the diagnosis of A-T, as previously discussed [5]. Recurrent upper respiratory infections due to immune deficiency [6] occur in ataxia telangiectasia, but the two older patients also presented with frequent diarrhea, which may represent an associated infectious disease specific to the region in Mali where the patients live. Increased cancer susceptibility has been associated with A-T [7], however, hemato-oncological examination showed no signs of malignancy in our patients. In addition, abdominal and inguinal echography showed no tumors. Although cases of A-T have been reported in populations with African ancestry [3, 8] and in North Africa [9–11], reports of this disease in sub-Saharan Africa have been limited to clinical characterization [12, 13]. We report here genetically confirmed A-T with a novel mutation in this region, and add to the global spectrum of this disease. Our study shows that hereditary neurological diseases may not be uncommon in this region of Africa, although limited expertise and lack of diagnostic tools might lead to their underestimation and neglect.

Epidemio-Clinical, Therapeutic and Evolutive Aspects of Aortic Dissection in the Cardiology Department in Poin “G” Hospital University Center Bamako

Objective: The work aimed at describing an epidemioclinical, therapeutic and evolutionary characteristics of patients hospitalized for aortic dissection in the cardiology department in Point “G” Hospital University Center in Bamako—Mali. Methodology: It was a descriptive cross-sectional study from January 2010 to February 2017 in the CHU Point G cardiology department, including all patients hospitalized during this period. Results: Of 6912 hospitalized patients, 23 patients were concerned by aortic dissection. The prevalence of aortic dissection was 0.33%. The most affected age group was 50 - 69 (43.5%) of patients. The predominance was male with a sex ratio of 4.75. The cardiovascular risk factors were high blood pressure (73.9%) and smoking (60.9%). The major functional signs were chest pain (65.2%) and dyspnea (65.2%). Asphygmy (56.5%) and breath of aortic insufficiency (60.9%) were the dominant physical signs. The electrocardiogram recorded sinus tachycardia with 86.9% of patients. The radiographic of the frontal thorax showed mediastina widening (73.9%). At echocardiography, dilatation of the ascending aorta was described with 73.9% and the intimal veil (47.8%). Pericardial effusion was observed with 26.1% of patients. In the thoracic angioscan, the aortic dissection gave 43.5% for type A and 56.5% for type B. The aneurysm of the aorta was abdominal with 21.7%, ascending portion (13.0%) and descending with 8.7%. Complications were dominated by heart failure (47.8%) and aneurysm of the aorta (34.8%). The lethality was 52.2%. Conclusion: Aortic dissection is a medical and surgical emergency with poor prediction.

Hypertension in Clinical Practice: Control Rate in Short Term and Associated Factors in the Cardiology Department of the University Hospital Gabriel Touré (UH-GT) in Bamako (Mali)

Introduction: Hypertension (HTN) is for many decades a worldwide major risk factor for cardiovascular disease.However, hypertension control rates are globally low in the world. Studies on observance have been published in Mali but there is to our knowledge no published data about HTN control rate. We therefore conducted this study to assess the control rate in short term after 3 months management and to look for factors associated with HTN control. Materials and Methods: This study designed as prospective was conducted in the cardiology department of the University Hospital Gabriel Toure (UH-GT) from March 24 to September 24, 2017. All outpatients aged 18 years and more who came for visit and with hypertension as diagnose were involved. All patients have consented to participate in the study. Sociodemographic and data on physical examination including measures for BP, height, weight, waist circumference (WC) and direct costs as reported by the patients were recorded. Patients were asked about medication discontinuation and if yes why and then they were informed about the need to take regularly medication. The concept of chronic disease was explained to them. A formulary served to collect data that were inserted into a Microsoft Access database and analyzed using SPSS version 18. After describing of sociodemographics and continuous variables, crosstabs and finally a logistic regression was performed to look for blood pressure control predictors. Results: There was no statistical difference in sociodemographics between older and newly diagnosed patients. At 3 months globally 40.90% (31.1 for old Patients and 09.8% for newPatients) of the sample were controlled (Figure 1). For old patients, hypertension control rate at inclusion was 12.78% and reached 49.44% at 3 months (Figure 2). After logistic regression only HTN duration was significant predictor with Odd-ratio of 0.365 [0.213 - 0.624] 95% CI and p-value patients as reference). During the study period therapeutic regimen remained unchanged in 73.1% (44.4 for old Patients and 28.7 for newPatients. Calcium channel blocker (CCB), diuretics (DIU) and ACE-inhibitors (ACE-I) were the most prescribed drugs without statistical difference between patients with and without blood pressure under control. Conclusion: Short term hypertension control rate is low and patient follow-up must incorporate information at each visit as well as information through others channels for preventing hypertension. The duration of hypertension was found to be predictor for hypertension control.

Cardiovascular Risk Factors (CVrf) in Rural and Urban Areas Mali: Data from the Step 2013 Survey

Background: Traditional cardiovascular risk factors (CVrf) like hypertension, diabetes, dyslipidemia, obesity, smoking have been studied extensively through theses in hospital studies. Therefore, recent published data from community based studies are rare in Mali. Available data are old justifying to perform a community based study on traditional CVrf in rural and urban areas. Materials and Methods: We retrospectively performed a study which data stemmed from the last STEPS survey carried out in 2013 in some rural and urban areas of Mali. We studied hypertension, diabetes, tobacco smoking, obesity based on body mass index, waist circumference and waist-to-hip ratio. After bivariates analyses, we conducted a logistic regression with rural/urban as dependent variable using SPSS as analysis software for this purpose. Results: Weight, height, WC and HC were higher in urban area with 69.77 Kg, 169.13 cm, 85.98 cm and 97.26 cm compared to 66.27, 165.42, 81.46 and 93.23 in rural area (p as more prevalent in urban area while elevated waist-to-hip ratio was more prevalent in rural area. But in logistic regression for female, the Odds for Tobacco smoking rural as reference was 0.334 [CI: 0.151 - 0.738] (p = 0.007) and that for WHr is 0.582 [CI: 0.415 - 0.815] (p p p = 0.038). Conclusion: Traditional cardiovascular risk factors have high prevalence in this study and need to be monitored with larger studies. Female predictors were raised waist circumference in favour of urban and tobacco smoking and waist-to-hip ratio in favour of urban dwellers. Male diabetes was the only predictor we found.

Hypertension (HTN) Knowledge and with Its Associated Factors: About 456 Outpatients Seen in Cardiology Department in University Hospital (UH) Gabriel Touré—Bamako (Mali)

Background: High Blood Pressure (HBP) is high prevalent among adult population in Bamako, but little is known about factors associated with knowledge. Methods: It was a cross-sectional study involving patients aged 15 years and more with a first classification in normal blood pressure (HTN-) and high blood pressure (HTN+), and Second classification inpatients without knowledge (who answered No) (K-) and patients with knowledge (who answered Yes) (K+). A logistic regression was performed to look up predictors among different variables. Results: The sample involved 456 patients with a mean age of 51.39 years and 65.1% of female. The age group 45 - 59 years old made 32.5% and unschooled patients 60.3%. Patients with HBP accounted for 69.7% and those reporting to know about it 67.3%. HTN- and HTN+ differed significantly except for HR, height, sex and level of schooling. HBP prevalence increased with age up to 74 years. Regarding knowledge, sex, age group and number of FDRs did not differ significantly. High education level and duration of HBP was predictive of knowledge with an OR of 1.186 [CI 0.058 - 0.796] and 1.192 [CI 0.332 - 4.275] respectively. Conclusions: Our study provided data on HBP knowledge among outpatients with high educational level and HBP duration associated with better knowledge on HBP.

Hypertension and Associated Factors in Rural and Urban Areas Mali: Data from the STEP 2013 Survey

Background Our study aims to estimate hypertension (HTN) prevalence and its predictors in rural and urban area. Methods We conducted a cross-sectional population-based study involving subjects aged 15 to 65 years. Collected data (sociodemographic, blood pressure, weight, height, and blood glucose) were analyzed using SPSS version 20. A logistic regression was conducted to look for factors associated with HTN. Results Mean was 47 years. High blood pressure (HBP) prevalence was 21.1 and 24.7%, respectively, in rural and urban setting. In rural area age group significantly predicted hypertension with age of 60 years having more-than-4-times risk of hypertension, whereas, in urban area age group, sex and body mass index were predictors with OR: HTN raising from 2.06 [1.24–3.43] for 30–44 years old to 7.25 [4.00–13.13] for 60 years and more using <30 years as reference. Female sex was protective with OR of 0.45 [0.29–0.71] and using normal weight as reference OR for overweight was 1.54 [1.04–2.27] and 2.67 [1.64–4.36] for obesity. Conclusion Hypertension prevalence is high and associated factors were age group in rural area and age group, female sex, and body mass index in urban area.

Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians

Introduction Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron (SMN) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. Objective To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. Material and Methods We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula (SMN1 copy number + 0.2 ∗ SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. Results We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤ 2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression < 2 and would be at risk of ALS and the disease onset was as early as 16 years old. All 15 patients were male and some were physically handicapped within 1–2 years in the disease course. Conclusion Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.