Les anomalies oculomotrices dans la dystrophie musculaire oculopharyngée

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Evaluation de la ventilation non invasive à domicile dans la dystrophie myotonique de type 1

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

HTLV-1-associated inflammatory myopathies: low proviral load and moderate inflammation in 13 patients from West Indies and West Africa.

International audienceThe Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients' PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases

Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing

International audienceDefects in TRIM32 were reported in limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and in Bardet-Biedl syndrome. Few cases have been described to date in LGMD2H/STM, but this gene is not systematically analysed because of the absence of specific signs and difficulties in protein analysis. By using high-throughput variants screening techniques, we identified variants in TRIM32 in two patients presenting nonspecific LGMD. We report the first case of total inactivation by homozygous deletion of the entire TRIM32 gene. Of interest, the deletion removes part of the ASTN2 gene, a large gene in which TRIM32 is nested. Despite the total TRIM32 gene inactivation, the patient does not present a more severe phenotype. However, he developed a mild progressive cognitive impairment that may be related to the loss of function of ASTN2 because association between ASTN2 heterozygous deletions and neurobehavioral disorders was previously reported. Regarding genomic characteristics at breakpoint of the deleted regions of TRIM32, we found a high density of repeated elements, suggesting a possible hotspot. These observations illustrate the importance of high-throughput technologies for identifying molecular defects in LGMD, confirm that total loss of function of TRIM32 is not associated with a specific phenotype and that TRIM32/ASTN2 inactivation could be associated with cognitive impairment

ANO5 gene analysis in a large cohort of patients with anoctaminopathy:confirmation of male prevalence and high occurrence of the common exon 5 gene mutation

Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non-Northern European populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyperCKaemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20%-25% in unselected undiagnosed cases