Congenital myasthenic syndromes by Epsilon subunit mutations: Phenotypic profiles of 17 Algerian families.

Background: Congenital myasthenic syndromes (CMS) are a heterogeneous group of rare genetic disorders. The acetyl choline receptor contains five subunits, with a predominance of mutations affecting the epsilon subunit gene called cholinergic receptor nicotinic epsilon (CHRNE) gene.

Objective: To study the clinical phenotype of 17 families with CHRNE gene mutations.

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).

[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).

In-vitro immunomodulatory effects of nicotine on Nitric Oxide, interleukin 1β and interleukin 37 production in human peripheral blood mononuclear cells (PBMC) from patients with Behçet disease.

Behçet's disease is a chronic systemic inflammatory disorder associated with a cytokine profile disruption and increased nitric oxide levels. In our current study we sought to evaluate the in-vitro modulatory effect of nicotine, the principal alkaloid of tobacco, on nitric oxide (NO), interleukin 1β (IL-1β) and interleukin 37 (IL-37) production during Behçet's disease. Peripheral blood mononuclear cells cultures were performed with or without nicotine (200 μg/ml).

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.

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.

Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia.

Background: Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with great genetic and phenotypic heterogeneity, over 30 genes/loci have been associated with more than 20 different clinical forms of ARCA. Genetic heterogeneity combined with highly variable clinical expression of the cerebellar symptoms and overlapping features complicate furthermore the etiological diagnosis of ARCA. The determination of the most frequent mutations and corresponding ataxias, as well as particular features specific to a population, are mandatory to facilitate and speed up the diagnosis process, especially when an appropriate treatment is available.

Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.

The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents.

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found.

Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients.

Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX). We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade.

ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41.