Innovative Therapeutic Approaches in Congenital Myasthenic Syndromes.

Background And Objectives: To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs.

Methods: Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study).

Distal hereditary motor neuropathies.

Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous hereditary disorders characterized by a slowly progressive distal pure motor neuropathy. Electrophysiology, with normal motor and sensory conduction velocities, can suggest the diagnosis of dHMN and guide the genetic study. More than thirty genes are currently associated with HMNs, but around 60 to 70% of cases of dHMN remain uncharacterized genetically.

[Congenital myasthenic syndromes with kinetic abnormalities of the acetylcholine receptor].

Congenital myasthenic syndromes (CMS) are genetically and phenotypically very heterogeneous conditions resulting in a defect in the neuromuscular transmission. Post-synaptic forms are the most frequent CMSs, and acetyl choline receptor (low expressor) deficiency is the most commonly involved pathophysiological mechanism. CMS with kinetic abnormalities of the acetylcholine receptor (AChr) are much rarer and can give rise to potentially life-threatening phenotypes.

[The high phenotypic variability of RYR1 gene mutations].

The RYR1 gene encodes the ryanodine-receptor 1, a key protein in the excitation-contraction coupling that takes place in muscle fibers. This receptor is the main channel responsible for calcium release from the endoplasmic reticulum [1]. A number of clinical phenotypes are linked to various mutations in this large gene as shown in a compilation established by ORPHANET (see table).

The methylenetetrahydrofolate reductase C677T and A1298C genetic polymorphisms and plasma homocysteine in Alzheimer's disease in an Algerian population.

Background: The etiology of Alzheimer's disease (AD) is multifactorial. The most important challenge of research is the identification of potential biomarkers associated with AD pathogenesis that may significantly contribute to early diagnosis of the disease. We aim to explore an eventual association of the C677T and A1298C genetic polymorphisms in the gene with AD risk in an Algerian population.

Moderate phenotype of a congenital myasthenic syndrome type 19 caused by mutation of the COL13A1 gene: a case report.

Background: Congenital myasthenic syndromes caused by mutations in the COL13A1 gene are very rare and have a phenotype described as severe. We present the first case of congenital myasthenic syndrome described in Algeria and the Maghreb with a new mutation of this gene.

Case Presentation: We present an 8-year-old Algerian female patient, who presented with a moderate phenotype with bilateral ptosis that fluctuates during the day and has occurred since birth.

Clinical management and disease-modifying treatment for amyotrophic lateral sclerosis in African hospital centers: the TROPALS study.

To assess the availability of health workers and medications for clinical management of amyotrophic lateral sclerosis (ALS) in African hospital centers. Availability and affordability analyses of disease-modifying treatments were performed. : A multicenter observational study involving African hospitals was conducted.

NTRK1 gene-related congenital insensitivity to pain with anhidrosis: a nationwide multicenter retrospective study.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease resulting from mutations in the NTRK1 gene encoding the neurotrophic tyrosine kinase-1 receptor. In this multicenter observational retrospective study, we investigated CIPA patients identified from French laboratories sequencing the NTRK1 gene, and seven patients were identified. Patients originated from France (2), Suriname (2), Mali (1), Kazakhstan (1), and Algeria (1).

Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.

Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76).

Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.

Background: The penetrance of leucine rich repeat kinase 2 (LRRK2) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in LRRK2-associated PD is unknown.

Objectives: The objective of this study is to evaluate the association of regular NSAID use and LRRK2-associated PD.

A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs).

Objective: Charcot-Marie-Tooth (CMT) disease 4B1 and 4B2 (CMT4B1/B2) are characterized by recessive inheritance, early onset, severe course, slowed nerve conduction, and myelin outfoldings. CMT4B3 shows a more heterogeneous phenotype. All are associated with myotubularin-related protein (MTMR) mutations.

Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study.

Objective: We describe and compare the sociodemographic and clinical features, treatments, and prognoses and survival times of patients with amyotrophic lateral sclerosis (ALS) in Africa.

Methodology: We conducted a multicentre, hospital-based cohort study in Africa. Patients with ALS diagnosed in the neurology departments of participating hospitals from 2005 to 2017 were included.

Updating the classification of inherited neuropathies: Results of an international survey.

Objective: The continual discovery of disease-causing gene mutations has led to difficulties in the complex classification of Charcot-Marie-Tooth diseases (CMT) that needs to be revised.

Methods: We recently published a proposal to update the classification of inherited neuropathies. The reactions from colleagues prompted us to diffuse the proposal and ask people if they would be ready for such a change.

Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1.

Importance: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels.

Objectives: To improve the clinical, biomarker, and molecular delineation of AOA1 and provide genotype-phenotype correlations.

Design, Setting, And Participants: This retrospective analysis included the clinical, biological (especially regarding biomarkers of the disease), electrophysiologic, imaging, and molecular data of all patients consecutively diagnosed with AOA1 in a single genetics laboratory from January 1, 2002, through December 31, 2014.

Nerve Biopsy Is Still Useful in Some Inherited Neuropathies.

In hereditary neuropathies, next-generation sequencing techniques are producing a vast number of candidate gene mutations that need to be verified or excluded by careful genotype-phenotype correlation analysis. In most cases, clinical acumen is still important but needs to be combined with data from nerve conduction studies and, in some cases, from nerve biopsy examinations. Indeed, characteristic clinical, electrophysiological, and sometimes pathological features may be suggestive of a particular subtype of Charcot-Marie-Tooth (CMT) disease.

History and current difficulties in classifying inherited myopathies and muscular dystrophies.

The wide spectrum of hereditary muscular disorders leads to unavoidable difficulties in their classification, even for specialists. For this reason, new proposals are required that would ultimately replace our current rather complex classifications by a simpler structure. Our proposal will be limited to dystrophic and non-dystrophic myopathies (excluding metabolic disorders, mitochondriopathies, and channelopathies) for which similar proposals would also be relevant.

DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study.

Background: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance.

Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases.

Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series.