Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis

A rapid polymerase chain reaction-based test for screening Steinert's disease (DM1)

Myotonic dystrophy (DM) is a multisystemic neuromuscular disorder caused by a dynamic mutation of (CTG) trinucleotide repeats in the 3′ untranslated region of the myotonic dystrophy protein kinase gene (DMPK). The aim of the present study was to establish the use of polymerase chain reaction (PCR)-based simple and rapid method for initial sample screening. Only a minority of samples were tested positive with the above method and need to be detected by tri primer (TP)-PCR and Southern blotting which is more time consuming and involves use of radioactive material. This study concerned 24 patients from nine families with a clinical diagnosis of the DM1. DNA extracted from the blood was used for amplification of the triplet repeat sequences at the DMPK loci. We obtained two bands for the normal subjects and one band for patients corresponding to normal DMPK allele, confirmed by the TP-PCR and the Southern blot. This rapid test for initial screening of samples for the presence of DMPK mutations is economical and reliable method. This method reduces the number of samples needing TP-PCR and Southern blotting

A novel mutation in the ABCD1 gene of a Moroccan patient with X-linked adrenoleukodystrophy: case report

International audienceAbstractBackgroundX-linked adrenoleukodystrophy (X-ALD; OMIM: 300100) is the most common peroxisomal disease caused by mutations in the ATP-binding cassette, sub-family D member 1 gene or ABCD1 (geneID: 215), the coding gene for the adrenoleukodystrophy protein (ALDP), which is an ATP-binding transport protein associated to an active transport of very long chain fatty acids (VLCFAs). Dysfunction of ALDP induces an accumulation of VLCFAs in all tissues leading to a neurodegenerative disorder that involves the nervous system white matter.Case presentationIn our case report, magnetic resonance imaging (MRI) as well as the high levels of VLCFAs prompted the diagnosis the X-ALD. Molecular analysis of ABCD1 gene have shown a pathogenic homozygous nonsense mutation (c.1677C > G; p.(Tyr559*)) in exon 7.ConclusionThus, we identified here a novel mutation in the ABCD1 gene in a Moroccan patient causing X-linked adrenoleukodystrophy

A Proteomic Approach for the Involvement of the GAPDH in Alzheimer Disease in the Blood of Moroccan FAD Cases

© 2014, Springer Science+Business Media New York. Several articles have highlighted the potential involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in neurodegeneration by showing a non-glycolytic activity of GAPDH specifically in the brains of subjects with Alzheimer’s disease (AD). The novel aim of this study was to elucidate the critical role of GAPDH and its interaction with β-amyloid in the blood of Moroccan patients with familial AD (FAD) carrying presenilin mutations and in sporadic late onset AD (LOAD). Our results show a significant decrease in the activity of GAPDH in blood samples from patients with FAD as compared to sporadic cases and healthy controls. The expression level of GAPDH in brain specimens from mutant tau transgenic mice and patients with FAD was unchanged as compared to healthy controls. In contrast, the expression level of GAPDH in blood samples from mutant tau transgenic mice and patients with FAD was decreased as compared to sporadic cases and healthy controls. Moreover, there is an accumulation of β-amyloid aggregates in the blood samples of patients with FAD and an increase in amyloid fibrils in both the blood and brain samples of these patients. Our study adds new insight to previous ones by showing the involvement of GAPDH in AD, which may influence the pathogenesis of this neurodegenerative disease

Chorea-ballismus in acute non-ketotic Hyperglycaemia

Diabetic patients during hyperglycaemic crises may present a rare syndrome characterised by a typical triad: unilateral involuntary movements (hemichoreahemiballism), radiological contralateral striatal abnormality, and rapid resolution of symptoms after glycae mic correction. This study reports a series of patients showing less usual aspects and also discusses the pathophysiology of this clinical-radiological syndrome. We included in this study four patients presenting choreic or ballic involuntary movements and in whom aetiological assessment revealed frank non-ketotic hyperglycaemia, without other abnormalities that could explain the movement disorder. All the patients underwent CT or MR brain imaging. The typical triad was present in only one case. Less classical aspects were more frequently found: movement disorders revealed diabetes in two patients and one patient had generalised chorea and strictly normal neuroimaging. Correction of blood glucose was not sufficient to improve symptoms in two cases. In one, abnormal movements persisted despite treatment with tetrabenazine. The clinical, radiological and outcome spectrum of the syndrome of chorea-ballismus induced by non-ketotic hyperglycaemia is heterogeneous and not restricted to a typical tria

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era