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1.
Rev Epidemiol Sante Publique ; 70(2): 75-81, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35337700

RESUMO

INTRODUCTION: Epilepsy is one of the most common chronic neurological diseases. In Morocco, it is the second most common reason for consulting a neurologist. Its prevalence was estimated in Casablanca in 1998 at 1.1%. This study was carried out with the aim of evaluating, on the one hand, the consumption of antiepileptics and, on the other hand, the impact of their generic drugs on the pharmaceutical market between 2008 and 2018 in Morocco. MATERIALS AND METHODS: We used sales data for antiepileptic drugs collected from the Moroccan subsidiary of IQVIA, a multinational healthcare data science company, and we converted them into a defined daily dose (DDD/1000 inhabitants). RESULTS: The consumption of antiepileptic drugs increased from 442 to 641 DDD/1000 inhabitants between 2008 and 2018, all molecules combined, recording a 45% increase in the period studied. From an economic point of view, the calculation of the average cost of DDD, all molecules combined, gives an average cost of 2.42 dollars/DDD in 2018 versus 3.53 dollars/DDD in 2008 (1 dirham = 0.11 dollar), which corresponds to a decrease of -30%. This is due mainly to the introduction of generic drugs. CONCLUSION: These results show that while the average cost of a DDD has decreased, the consumption of antiepileptics has increased in Morocco over the years. Several events that have marked the drug market in Morocco have contributed to this trend, including the arrival on the market of several new molecules indicated for the treatment of epilepsy, the decrease in drug prices in 2014 and the policy of promoting generic drugs.


Assuntos
Anticonvulsivantes , Medicamentos Genéricos , Anticonvulsivantes/uso terapêutico , Comércio , Custos de Medicamentos , Uso de Medicamentos , Medicamentos Genéricos/uso terapêutico , Humanos , Marrocos/epidemiologia
2.
Am J Hum Genet ; 98(5): 1038-1046, 2016 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-27153400

RESUMO

Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms.


Assuntos
Axônios/patologia , Calpaína/genética , Predisposição Genética para Doença/genética , Neurônios Motores/patologia , Paraplegia Espástica Hereditária/genética , Adulto , Animais , Encéfalo/fisiologia , Caenorhabditis elegans/genética , Movimento Celular/genética , Modelos Animais de Doenças , Drosophila melanogaster/genética , Feminino , Humanos , Masculino , Neurônios Motores/citologia , Adulto Jovem , Peixe-Zebra/genética
3.
BMC Cardiovasc Disord ; 19(1): 117, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31096916

RESUMO

BACKGROUND: Postoperative bleeding in cardiovascular surgery is a frequent and complicated situation for the surgical team, and may also be responsible for significant hospital expenditures. Fibrin glue are indicated in surgery to improve hemostasis when conventional techniques such as compression, sutures or electrocoagulation are insufficient. Through this study, we tried to study the contribution of fibrin glue to the improvement of the clinical parameters (volume of postoperative bleeding, length of stay in intensive care, volume of blood transfusion ...) in two populations having undergone cardiac surgery, one in which we used the fibrin glue and one without fibrin glue. METHODS: This was a retrospective cohort study conducted in the cardiovascular surgery department of our Hospital in Rabat between June 2012 and June 2015. Fibrin glue (Tissucol® of BAXTER) was used in one group with an haemostatic aim. The pre and post-operative clinical data of the patients were analyzed and compared with data from patients who were operated without the use of fibrin glue because it was not yet available in the hospital. The clinical parameters were collected analyzed using the SPSS 13.0 software. RESULTS: One hundred ten patients were included in this study. The fibrin glue was used intraoperatively in 55 patients and not used in 55 patients. 43 (39.1%) had cyanogenic diseases and 67 (60.9%) had non-cyanogenic pathologies. The volume of transfused red blood cells was lower in patients in whom we used biological glue (p = 0.005), as well as the number of days spent in intensive care (p = 0.02). However, the difference was not significant between the two groups for other parameters such as bleeding volume per kg, the number of units of fresh frozen plasma and the platelet units count transfused. CONCLUSIONS: The results we found show that fibrin glue reduces the duration of hospitalization in resuscitation and reduces the number of units of transfused red blood cells to patients after surgery. However, it does not reduce significantly the total postoperative bleeding volume per weight, the number of fresh frozen plasma units or platelets units transfused. The fibrin glue could therefore be of moderate benefit in pediatric cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cianose/etiologia , Adesivo Tecidual de Fibrina/uso terapêutico , Cardiopatias Congênitas/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Adesivos Teciduais/uso terapêutico , Criança , Pré-Escolar , Cianose/diagnóstico , Transfusão de Eritrócitos , Feminino , Adesivo Tecidual de Fibrina/efeitos adversos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Tempo de Internação , Masculino , Marrocos , Plasma , Transfusão de Plaquetas , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Fatores de Tempo , Adesivos Teciduais/efeitos adversos , Resultado do Tratamento
4.
Am J Hum Genet ; 91(6): 1051-64, 2012 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-23176821

RESUMO

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function.


Assuntos
Ácidos Graxos/metabolismo , Mitocôndrias/enzimologia , Mitocôndrias/genética , Paraplegia Espástica Hereditária/enzimologia , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Criança , Pré-Escolar , Mapeamento Cromossômico , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Família 2 do Citocromo P450 , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Fenótipo , Fosfolipases/genética , Fosfolipases/metabolismo , Transporte Proteico , Adulto Jovem
5.
J Med Genet ; 51(2): 137-42, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24319291

RESUMO

BACKGROUND: Hereditary spastic paraparesis (HSP) (syn. Hereditary spastic paraplegia, SPG) are a group of genetic disorders characterised by spasticity of the lower limbs due to pyramidal tract dysfunction. Nearly 60 disease loci have been identified, which include mutations in two genes (KIF5A and KIF1A) that encode motor proteins of the kinesin superfamily. Here we report a novel genetic defect in KIF1C of patients with spastic paraparesis and cerebellar dysfunction in two consanguineous families of Palestinian and Moroccan ancestry. METHODS AND RESULTS: We performed autozygosity mapping in a Palestinian and classic linkage analysis in a Moroccan family and found a locus on chromosome 17 that had previously been associated with spastic ataxia type 2 (SPAX2, OMIM %611302). Whole-exome sequencing revealed two homozygous mutations in KIF1C that were absent among controls: a nonsense mutation (c.2191C>T, p.Arg731*) that segregated with the disease phenotype in the Palestinian kindred resulted in the entire absence of KIF1C protein from the patient's fibroblasts, and a missense variant (c.505C>T, p.Arg169Trp) affecting a conserved amino acid of the motor domain that was found in the Moroccan kindred. CONCLUSIONS: Kinesin genes encode a family of cargo/motor proteins and are known to cause HSP if mutated. Here we identified nonsense and missense mutations in a further member of this protein family. The KIF1C mutation is associated with a HSP subtype (SPAX2/SAX2) that combines spastic paraplegia and weakness with cerebellar dysfunction.


Assuntos
Doenças Cerebelares/genética , Cinesinas/genética , Paraparesia Espástica/genética , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Consanguinidade , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Ligação Genética , Células HEK293 , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Adulto Jovem
6.
Tunis Med ; 93(6): 365-70, 2015 Jun.
Artigo em Francês | MEDLINE | ID: mdl-26644099

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common disease of the motor neuron disease. Its etiology remains unknown but several studies incriminate the environmental factors in its genesis. THE AIM: of this study was to describe the epidemiological, clinical and environmental aspects of ALS in Moroccan population. METHODS: 60 ALS patients were recruited over a period of 5 years from January 2008 to September 2012. Patients were evaluated by detailed record of exploitation. Statistical analysis was performed using SPSS 13.0. RESULTS: The average age of the population was 52.1 ± 11.2 years with a sex ratio of M/F = 1.5. The average age of onset was 50 ± 11.7 years. In the group of patients exposed to toxic a significantly higher proportion of solvent exposure was found (p = 0.02). However there was no significant association with exposure to heavy metals, pesticides, or with toxic and eating habits. ALS is more frequent in the west region of Morocco (p = 0.03). CONCLUSIONS: The positive association between exposure to solvents and ALS found in our population has been reported in the literature. The frequency of the ALS early west region suggests may be environmental or genetic origin. These results are preliminary and require a multicenter study to have more data and better highlight the environmental characteristics of ALS in the Moroccan population.


Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Solventes/toxicidade , Adulto , Idade de Início , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Metais Pesados/toxicidade , Pessoa de Meia-Idade , Marrocos/epidemiologia , Praguicidas/toxicidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
8.
Cureus ; 16(5): e60588, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38894759

RESUMO

Paget's disease of the bone (PDB) is a benign osteodystrophy of the elderly characterized by excessive remodeling of bone tissue, mainly in the pelvis, femur, and skull. Its neurological manifestations are numerous and affect both the central and peripheral nervous systems. As headaches are often reported, epileptic seizures remain exceptional. We report the case of a 75-year-old female patient with a history of chronic worsening headache who was admitted to the emergency department for the first episode of a seizure. Brain imaging revealed heterogeneous bone thickening and circumscribed skull osteoporosis. Bone scintigraphy showed pagetoid lesions restricted to the skull and face. Alkaline phosphatases increased. The rest of the biological work-up and the cerebrospinal fluid study ruled out other metabolic causes or central nervous system infections. The patient was treated with bisphosphonates and anti-convulsive treatment. The evolution was satisfactory, with progressive improvement in headache and seizure control, even several months after discontinuation of anti-seizure medication. Our case report highlights the importance of exploring chronic headaches in the elderly, not only in search of lesions of the cerebral parenchyma but also of the structures containing them, in this case, the skull.

9.
Genet Test Mol Biomarkers ; 28(6): 257-262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38721948

RESUMO

Background: Wolfram syndrome (WFS) is an autosomal recessive disorder that often leads to diabetes, optic atrophy, and sensorineural hearing loss. The aim of this study was to determine the clinical characteristics and the genetic cause of the first two Moroccan families presenting with WFS. Methods: The clinical features of five members of two WFS families were evaluated. Whole-exome sequencing was conducted to explore the underlying genetic cause in the affected patients. Results: Two homozygous variants in the WFS1 gene were identified, each in one of the two families studied: a missense c.1329C>G variant (p.Ser443Arg) and a nonsense mutation c.1113G>A (p.Trp371Ter). These variants affected conserved amino acid residues, segregated well in the two families, and are absent from genetic databases and in controls of Moroccan origin. Bioinformatics analysis classified the two variants as pathogenic by in silico tools and molecular modeling. Conclusion: Our study identified for the first time two variants in Moroccan patients with WFS that extends the mutational spectrum associated with the disease.


Assuntos
Proteínas de Membrana , Mutação de Sentido Incorreto , Linhagem , Síndrome de Wolfram , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Códon sem Sentido/genética , Sequenciamento do Exoma/métodos , Homozigoto , Proteínas de Membrana/genética , Marrocos , Mutação , Mutação de Sentido Incorreto/genética , Síndrome de Wolfram/genética , Adulto Jovem
10.
J Mol Neurosci ; 73(6): 391-402, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37256495

RESUMO

Parkinson's disease (PD) is a neurodegenerative movement disorder which can be either familial or sporadic. While it is well known that monogenic mutations are not a very common cause of PD, GWAS studies have shown that an additional fraction of the PD heritability could be explained by rare or common variants. To identify the rare variants that could influence the risk of PD in the Moroccan population, a cohort of 94 sporadic PD patients negative for the LRRK2 G2019S mutation was subjected to NGS gene panel sequencing, and gene dosage using the MLPA method. Mean age of onset at enrollment was 51.7 ± 11.51 years, and 60% of patients were men. We identified 70 rare variants under 0.5% of frequency in 16 of the 20 genes analyzed, of which 7 were novel. Biallelic disease-causing variants in genes with recessive inheritance were found in 5 PD cases (5.31%), whereas 13 patients (13.8%) carried likely pathogenic variants in genes with dominant inheritance. Moreover, 8 patients (8.5%) carried a single variant in MAPT or POLG, whereas co-occurrence of rare variants involving more than one gene was observed in 28 patients (30%). PD patients with variants in recessive genes had a younger mean age at onset than patients with dominant ones (33.40 (12.77) vs. 53.15 (6.63), p < 0.001), while their clinical features were similar. However, patients with rare variants in the risk factor genes or in more than one gene tended to have less resting tremor (p < 0.04), but more dystonia (p < 0.006) and dementia (p < 0.002) than those without any rare variants in known PD-associated genes. Our results showed a significant enrichment of rare variants particularly in LRRK2, VPS13C, POLG, and MAPT and underline their impact on the risk of sporadic form of the disease.


Assuntos
Doença de Parkinson , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Doença de Parkinson/genética , Doença de Parkinson/patologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mutação , Estudo de Associação Genômica Ampla , Genes Recessivos , Predisposição Genética para Doença
11.
BMC Med Genet ; 13: 18, 2012 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-22436252

RESUMO

BACKGROUND: Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern. METHODS: All family members underwent neurological and radiological examinations. A genome wide search was conducted in this family using the ABI PRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate genes within the region linked to the disease were screened for mutations by direct sequencing. RESULTS: Evidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis of recombination events and LOD score calculation suggests linkage of the responsible gene in a genetic interval of 11 Mb located between D17S789 and D17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven candidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and GRIN2C, identified three missense mutations in the FDXR gene which were also found in a homozygous state in three healthy controls, suggesting that these variants are not disease-causing mutations in the family. CONCLUSION: A novel locus for leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome 17q24.2-25.3 in a consanguineous Moroccan family.


Assuntos
Transtornos Dismórficos Corporais/genética , Cromossomos Humanos Par 17/genética , Retinose Pigmentar/genética , Acidente Vascular Cerebral/genética , Adulto , Sequência de Bases , Mapeamento Cromossômico , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Marrocos , Análise de Sequência de DNA
12.
Am J Hum Genet ; 82(4): 992-1002, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18394578

RESUMO

Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous disorders. Both "uncomplicated" and "complicated" forms have been described with various modes of inheritance. Sixteen loci for autosomal-recessive "complicated" HSP have been mapped. The SPG15 locus was first reported to account for a rare form of spastic paraplegia variably associated with mental impairment, pigmented maculopathy, dysarthria, cerebellar signs, and distal amyotrophy, sometimes designated as Kjellin syndrome. Here, we report the refinement of SPG15 to a 2.64 Mb genetic interval on chromosome 14q23.3-q24.2 and the identification of ZFYVE26, which encodes a zinc-finger protein with a FYVE domain that we named spastizin, as the cause of SPG15. Six different truncating mutations were found to segregate with the disease in eight families with a phenotype that included variable clinical features of Kjellin syndrome. ZFYVE26 mRNA was widely distributed in human tissues, as well as in rat embryos, suggesting a possible role of this gene during embryonic development. In the adult rodent brain, its expression profile closely resembled that of SPG11, another gene responsible for complicated HSP. In cultured cells, spastizin colocalized partially with markers of endoplasmic reticulum and endosomes, suggesting a role in intracellular trafficking.


Assuntos
Proteínas de Transporte/genética , Doenças Cerebelares/genética , Cromossomos Humanos Par 14/genética , Disartria/genética , Transtornos Mentais/genética , Debilidade Muscular/genética , Retinose Pigmentar/genética , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Animais , Encéfalo/metabolismo , Proteínas de Transporte/análise , Proteínas de Transporte/metabolismo , Células Cultivadas , Criança , Retículo Endoplasmático/metabolismo , Endossomos/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Mutação , Linhagem , Mapeamento Físico do Cromossomo , Ratos , Síndrome , Dedos de Zinco/genética
13.
J Mol Neurosci ; 71(1): 142-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32557143

RESUMO

In the past two decades, genetic studies of familial forms of Parkinson's disease (PD) have shown evidence that PD has a significant genetic component. Indeed, 12 genes are strongly involved in PD causality, three of them having dominant inheritance and 9 causing early-onset autosomal recessive forms, including 3 with a typical PD and 6 with an atypical parkinsonism. The aim of this study was to determine the genetic basis of familial PD in Moroccan patients. We selected 18 Moroccan index case with familial forms of PD. Patients were first screened for exon-rearrangements by MLPA kit. They were then analyzed by gene panel next-generation sequencing (NGS). Functional variants with minor allele frequencies < 0.5% in public databases were considered potential candidate variants to PD. In the 18 PD patients with a positive family history that were analyzed, MLPA assays identified PRKN deletions in two patients: a homozygous exon 3-5 deletion and a heterozygous exon 4 deletion. Sixteen rare SNV were identified by NGS, four of them were novel. Seven mutations were categorized as pathogenic, five as likely pathogenic, two to be of uncertain significance, and 3 were predicted to be likely benign but may give a weaker pathogenic effect and could contribute to PD since they were found in late-onset PD patients. Rare or novel mutations that could be related to the disease were identified in 72% of these patients (13/18), including nine with bi-allelic pathogenic/likely pathogenic variants in genes causing recessive PD, particularly PRKN and PINK1. Mutations in genes with dominant inheritance were found in 4/18 patients (22%).


Assuntos
Mutação , Doença de Parkinson/genética , Adulto , Idade de Início , Idoso , Alelos , Consanguinidade , Feminino , Genes Dominantes , Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , Reação em Cadeia da Polimerase Multiplex , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/epidemiologia , Polimorfismo de Nucleotídeo Único , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Avaliação de Sintomas
15.
Med Sci (Paris) ; 36(4): 348-357, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32356711

RESUMO

Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet drugs is a priority in the fight against cardiovascular diseases-associated mortality. Aspirin and thienopyridine-based P2Y12 inhibitors are the main drugs currently used. These molecules target the initiation of platelets activation and are responsible for a moderate inhibitory action. Other antiplatelet agents, as glycoprotein (GP) IIb/IIIa antagonists, inhibit platelet aggregation independently of initial activation-associated pathways, but are responsible for increased hemorrhagic events. Regarding each antiplatelet agent's specific characteristics, the prescription of these drugs must take into account the type of cardiovascular event, the age of the patient, the past medical history, and the potential hemorrhagic adverse events. Thus, there is a need for the development of new molecules with a more targeted effect, maintaining optimal efficiency but with a reduction of the hemorrhagic risk, which is the principal limitation of these treatments.


TITLE: Antiplaquettaires actuels, en cours de développement et cibles thérapeutiques. ABSTRACT: Les maladies cardiovasculaires (MCV) sont la première cause de mortalité dans le monde. Les plaquettes jouent un rôle majeur dans le développement de ces maladies et la mise au point d'antiplaquettaires efficaces constitue une priorité dans le cadre de la lutte contre la mortalité liée aux MCV. L'aspirine et les médicaments de la famille des thiénopyridines sont les agents antiplaquettaires les plus utilisés actuellement. Ces médicaments ciblent des voies de signalisation impliquées dans l'initiation de l'agrégation, exerçant ainsi un effet antiplaquettaire modéré. D'autres médicaments aux effets plus importants, comme les molécules dirigées contre le récepteur GPIIb/IIIa, inhibent l'agrégation plaquettaire indépendamment de la voie de signalisation initiant l'activation plaquettaire, mais ils sont associés à des complications hémorragiques majorées. Étant données les caractéristiques spécifiques de chacun de ces agents antiplaquettaires, leur prescription nécessite de prendre en compte le type d'évènement cardio-vasculaire, l'âge et les comorbidités du patient traité et, bien sûr, les effets secondaires hémorragiques potentiels de la molécule qui est prescrite. Apparaît donc la nécessité de mettre au point de nouvelles molécules ayant un effet plus ciblé, gardant une efficacité optimale, mais permettant une réduction du risque hémorragique qui constitue la principale limite des médicaments antiplaquettaires.


Assuntos
Terapia de Alvo Molecular/tendências , Inibidores da Agregação Plaquetária/uso terapêutico , Terapias em Estudo/tendências , Aspirina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Hemorragia/induzido quimicamente , Humanos , Terapia de Alvo Molecular/métodos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Fatores de Risco , Terapias em Estudo/métodos
16.
Neurogenetics ; 10(1): 35-42, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18758830

RESUMO

We describe the clinical, radiographic, and genetic features of a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait. Six affected members of the family had partial complex seizures often associated with behavioral abnormalities. On MRI, three patients had a thickened irregular cortex in the lateral occipital lobes with small gyri. A high-density genome-wide scan with 10,000 SNPs established linkage by homozygosity mapping to a 14-Mb region on chromosome 6q16-q22. Candidate genes by function (TUBE1, GRIK2, GPRC6A, GPR6, NR2E1, MICAL1, and MARCKS) in this locus were screened for mutations.


Assuntos
Cromossomos Humanos Par 6 , Malformações do Desenvolvimento Cortical/genética , Adulto , Mapeamento Cromossômico , Consanguinidade , Análise Mutacional de DNA , Família , Feminino , Predisposição Genética para Doença , Humanos , Escore Lod , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/patologia , Malformações do Desenvolvimento Cortical/fisiopatologia , Pessoa de Meia-Idade , Marrocos , Polimorfismo de Nucleotídeo Único , Adulto Jovem
17.
Pan Afr Med J ; 33: 2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303947

RESUMO

Ischemic stroke can result from multiple etiologies. It can also be a complication of tuberculous meningoencephalitis and determine its outcome. stroke secondary to tuberculous meningoencephalitis, occurs in 30% cases in the basal ganglia region, unusually in the thalamus. The mechanism of stroke in this condition is vasculitis. We report an unusual case of bilateral thalamic infarcts complicating tuberculous meningoencephalitis. Ischemic stroke in tuberculous meningoencephalitis is unpredictable with poor prognosis despite antituberculous drug treatment, emphasising the importance of primary prevention, particularly in tuberculosis endemic areas.


Assuntos
Infarto Encefálico/etiologia , Meningoencefalite/complicações , Acidente Vascular Cerebral/etiologia , Tuberculose Meníngea/complicações , Adolescente , Antituberculosos/administração & dosagem , Infarto Encefálico/diagnóstico , Humanos , Masculino , Meningoencefalite/tratamento farmacológico , Meningoencefalite/microbiologia , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Tálamo/patologia , Tuberculose Meníngea/tratamento farmacológico
18.
Brain ; 130(Pt 4): 1062-75, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17347251

RESUMO

Charcot-Marie-Tooth disease is a genetically heterogeneous group of hereditary motor and sensory neuropathies. Three loci for the axonal autosomal recessive subgroup (ARCMT2) have been reported in 1q21 (CMT2B1, LMNA), 8q21 (CMT4A and CMT2K, GDAP1) and 19q13 (CMT2B2). We report here a clinical, electrophysiological, pathological and genetic study in 13 Moroccan families with ARCMT2 phenotypes. Clinical and electrophysiological examinations were performed in all index cases and 64 'at-risk' relatives. Thirty-one patients were clinically affected. A peroneal nerve biopsy was obtained from three patients. Four families were linked to the 1q21 locus, all had the LMNA R298C mutation. Six families were linked to the 8q21 locus, all had the GDAP1 S194X mutation. Founder effects for both mutations were suggested by the analysis of microsatellite markers close to the genes. The three remaining families were excluded from the three known loci. The electrophysiological findings were consistent with an axonal neuropathy. The clinical data show that in CMT2B1 the disease began most often in the second decade and progressed gradually from distal to proximal muscles. Three of our patients with the longest disease durations (>24 years) had also severe impairment in the scapular muscles. Reported here for the first time, this might be a hallmark of CMT2B1. Patients with CMT4A/2K had onset most often before the age of 2 years. Most had severe clubfoot from the beginning, one of the hallmarks of CMT4A/2K. None of our patients with CMT4A/2K had vocal cord paralysis. The clinical phenotype of the three families that are not linked to the three known loci presented some particularities that were not seen in those with known genetic defects. One family was characterized by late onset of the disease (>20 years) or a mild neuropathy that was diagnosed only when the family was examined. In a second family, dorsal scoliosis was the most prominent symptom. In the third family, symptoms began in the second decade with a moderate neuropathy associated with a pronounced scoliosis. These families illustrate the extent of clinical and genetic heterogeneity in ARCMT2.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Potenciais de Ação/fisiologia , Adolescente , Adulto , Axônios/fisiologia , Doença de Charcot-Marie-Tooth/etnologia , Doença de Charcot-Marie-Tooth/fisiopatologia , Criança , Pré-Escolar , Consanguinidade , Eletromiografia , Feminino , Efeito Fundador , Genes Dominantes/genética , Genótipo , Humanos , Lamina Tipo A/genética , Escore Lod , Masculino , Marrocos , Mutação/genética , Proteínas do Tecido Nervoso/genética , Condução Nervosa/fisiologia , Linhagem , Nervo Fibular/patologia , Fenótipo
19.
Case Rep Genet ; 2018: 8635698, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30581635

RESUMO

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder due to mutations in the lysosomal acid 3-galactosidase gene, GLB1. It is usually classified into three forms, infantile, juvenile, or adult, based on age at onset and severity of central nervous system involvement. Because of their broad clinical spectrum and their similarity to many other aetiologies, including inherited neurodegenerative and metabolic diseases, it is often difficult to diagnose such diseases. Recently, whole exome sequencing (WES) has become increasingly used when a strong hypothesis cannot be formulated based on the clinical phenotype. Here, we present three patients belonging to a consanguineous Moroccan family with a GM1-gangliosidosis with unusual clinical onset and atypical radiological presentation that had eluded diagnosis for over a decade. To identify the disease-causing mutation, we performed a whole exome sequencing and a chromosomal microarray genotyping in order to reduce the number of genetic variants to be interpreted, by focusing the data analysis only on the linked loci. The already known pathogenic missense mutation c.601G>A in GLB1 (p.R201C) was found at homozygous state in the proband V.1 and at heterozygous state in his father IV.1. The mutation was validated by Sanger sequencing and segregated in all the family members according to a recessive mode of inheritance. Outside of the linked loci, we found the EXOSC8 p.Ser272Thr mutation at heterozygous state in all the patients and their mother IV.2. This mutation was reported to cause pontocerebellar hypoplasia type 1C and could act as a modifying factor that exacerbates the brain atrophy of patients. Our study identified the first GLB1 mutation in North Africa in patients with unexpected brain-MRI outcomes extending the clinical spectrum of the GM1-gangliosidosis.

20.
Front Neurol ; 9: 170, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670566

RESUMO

BACKGROUND: Non-motor symptoms (NMSs) are a real burden in Parkinson's disease (PD). They may appear in early pre-symptomatic stage as well as throughout the disease course. However, their relationship with the deterioration of the patient's quality of life (QoL) is still under debate. This study aimed to investigate the prevalence of NMSs and their impact on the QoL in a cohort of Moroccan patients. METHODS: We carried out a cross-transactional study, where a total of 117 patients were submitted to a structured clinical interview and examination investigating motor and NMSs based on common and conventional scales. Motor symptoms were assessed by the UPDRS I-VI during ON condition. The NMSs were evaluated with common scales and their relationship with the QoL was investigated. RESULTS: The mean patient's age was 60.77 ± 11.36 years old, and the median disease duration was 6 years [2.5-9.5]. Motor's phenotype subtypes were the mixed form in 40.2% of patients, akinetic-rigid in 20.5% and a tremor-dominant form in 39.3%. The median Hoehn and Yahr staging was 2 [1-2.5]. Regarding NMSs, the most common were urinary dysfunctions (82.6%), sleep (80.6%), and gastrointestinal (80%) disorders. Other autonomic dysfunctions were also frequent: thermoregulatory dysfunctions 58.6%, cardiovascular troubles 50.9%, and sexual dysfunctions 47.9%. Depression was present in 47.9% and fatigue symptoms in 23.1%. The median score of SCOPA-AUT was 14 [7.75-21.80]. The median PD questionnaire 39-score index (PDQ39-SI) was 23.22% and the most affected dimension was "mobility." Univariate and multivariate analyses showed that the SCOPA-AUT score impacted the QoL (p = 0.001), especially the gastrointestinal (p = 0.007), and cardiovascular (p = 0.049) dimensions. CONCLUSION: Our data show that all patients have presented at least one NMS. Autonomic and sleep disorders were the most frequent, and in contrast to other studies, digestive and cardiovascular disorders were rather the factors influencing negatively the QoL of patients. Understanding the pathophysiology of these NMSs should be placed at the forefront in order to develop new therapeutic approaches by improving the QoL of PD patients.

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