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Source: Neuromuscular Disorders
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Total 1514 results found since Jan 2013.
FP.33 Ataluren treatment in 30-week-old dysferlinopathy mouse with nonsense mutation
In this study, we used the same mice at the age of 30-week-old, equivalent to early adulthood in humans.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: K. Seo, D. Kim, H. Lee, J. Shin Tags: LGMD Source Type: research
VP.67 A novel adult-onset vacuolar myopathy caused by a large expansion of the PLIN4 gene- clinical, histological and imaging data
We formerly reported Italian kindred with adult-onset autosomal dominant vacuolar myopathy with 19 affected individuals over four generations. Myopathology was characterized by rimmed autophagic vacuolation and distinctive immunohistochemical features including involvement of the ubiquitin-proteasome pathway. More recently, we identified the protein accumulating within the vacuoles and pinpoint, with the use of long-read sequencing, a large coding expansion in the PLIN4 gene, member of the perilipins ’ family.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: L. Maggi, S. Gibertini, E. Iannibelli, A. Gallone, C. Bragato, S. Bonanno, F. Blasevich, R. Mantegazza, M. Mora, A. Ruggieri Source Type: research
VP.66 CRISPR/Cas9-targeted single molecule long-read sequencing reveals allelic microheterogeneity of triplet repeat expansion in oculopharyngodistal myopathy
Oculopharyngodistal myopathy (OPDM) is a hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia and predominantly distal muscle weakness. To date, CGG repeat expansion in 5 ’UTR of LRP12, GIPC1, NOTCH2NLC are known to be causative. Its pathogenesis has been suggested to be toxicities of the expanded RNAs or repeat-associated translated proteins, although it remains controversial. To elucidate the pathomechanism in OPDM, it is important to know precise sequences of ex panded repeats.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: N. Eura, S. Noguchi, M. Ogasawara, A. Iida, S. Hayashi, I. Nishino Source Type: research
VP.65 Screening of small molecules for activation of GNE protein carrying non-catalytic site mutation based on molecular docking simulation
GNE myopathy is an autosomal recessive distal myopathy caused by pathogenic variants in GNE gene, which encodes a protein having two enzymatic activities, UDP-GlcNAc 2-epimerase and ManNAc kinase on sialic acid biosynthesis. We have identified a variant, c.620A>T (p.D207V), with which majority of the homozygotes are healthy, while compound heterozygotes develop myopathy. Notwithstanding, the identified three affected homozygotes had no additional variation in the GNE gene nor in genes in sialic acid biosynthetic pathway, while their sialylation was mildly, but certainly decreased.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: W. Yoshioka, K. Yamamoto, S. Hayashi, M. Sekijima, I. Nishino, S. Noguchi Source Type: research
P.157 Dominant HSPB6 mutation in a myopathy patient
HSPB6 (also known as Hsp20) is a small heat-shock protein (sHSP) showing highest expression is skeletal, cardiac and smooth muscles. In contrast to most sHSPs, HSPB6 does not readily assemble into large oligomers on its own. However, it heterodimerizes with HSPB1 and hetero-oligomerizes with HSPB1 and αB-crystallin (CRYAB, HSPB5), modulating their oligomer size and chaperone activity. HSPB6 may also be involved in BAG3-mediated autophagy.Mutations in several sHSPs lead to neuromuscular disease. While rare missense variants in HSPB6 have been associated with cardiomyopathy, the gene has not been previously linked to skeletal muscle disease.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: J. Sarparanta, P. Jonson, A. Vihola, H. Luque, A. Vainio, R. Villar-Quiles, T. Stojkovic, N. Romero, B. Eymard, B. Udd Source Type: research
P.156 Novel repeat expansions in PLIN4 in two Spanish families suffering from autosomal dominant distal myopathy with unique pathological features
Perilipins are a family of proteins that coat the surface of lipid droplets and regulate lipid turnover. Perilipin 4, encoded by PLIN4 on chr 9, is highly expressed in skeletal muscle where it mainly localizes to the subsarcolemmal regions of type 1 myofibres. An expansion of the perilipin 4 amphipathic domain (40 x 99 repetitive sequences in exon 3) was recently identified in a family suffering from an autosomal (AD) distal vacuolar myopathy. We aim to describe two unrelated Spanish families suffering from a highly similar distal myopathy caused by two different size repeat expansions in PLIN4, respectively.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: M. Oliv é, I. Stevanovski, L. González Quereda, G. Morris, A. Segarra-Casas, B. Rodriguez-Santiago, P. Gallano, R. Alvarez, A. Vesperinas, B. San Millan, C. Navarro, G. Ravenscroft, I. Illa, I. Deveson, E. Gallardo Source Type: research
P.155 Recurring homozygous ACTN2 variant (p.Arg506Gly) cause a recessive, adult-onset myofibrillar myopathy
ACTN2, encoding alpha-actinin-2, is essential for sarcomeric function in cardiac and skeletal muscle. Pathogenic ACTN2 variants are a known cause for cardiomyopathies without muscle manifestations. Recently specific dominant variants have been reported as a rare cause of core myopathy, although the precise pathomechanism remains to be elucidated. A tentative recessive ACTN2 manifestation has also been proposed previously. Here we report four patients from three families with a recurring biallelic c.1516A>G (p.Arg506Gly) ACTN2 variant manifesting with adult-onset, asymmetric, progressive, proximal and distal lower extremity...
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: S. Donkervoort, P. Mohassel, M. O'Leary, T. Hartley, T. Mozaffar, M. Saporta, D. Dyment, C. Austin-Tse, S. Verma, K. Hurth, J. Warman-Chardon, A. O'Donnell-Luria, C. B önnemann Source Type: research
P.154 A novel TIA1 frameshift variant in a dominant myopathy family
The proband is a 58-year-old woman with a 6-7-year history of wasting of the thumb muscles. The clinical phenotype resembles Welander distal myopathy (WDM). The family history suggests autosomal dominant inheritance: the proband's father had abnormal gait in his 30s, developed weak hands in his 50s, and required AFOs by his 70s. Two paternal uncles and one paternal aunt were similarly affected and clinically examined more than 30 years ago. These relatives are now deceased, preventing genetic analysis.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: J. Sarparanta, P. Jonson, A. Vihola, H. Luque, S. Brady, B. Udd Source Type: research
P.153 Pilot trial of sialyllactose in patients with GNE myopathy
In this study, we administered 6 ’-sialyllactose (6SL) as an alternative source of sialic acid to the patients with GNE myopathy.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: Y. Park, J. Choi, L. Kim, J. Shin Source Type: research
P.152 The novel ANXA11 variant p.Asp40Ile in a childhood-onset oculopharyngeal muscular dystrophy shows the pathogenic relevance of Asp40 in ANXA11 disorders
ANXA11 mutations have been associated with two different adult-onset conditions: amyotrophic lateral sclerosis and inclusion body myopathy/multisystem proteinopathy. The pathogenic variant p.Asp40Gly has been identified in individuals with ALS and, more recently, p.Asp40Tyr in patients with multisystem proteinopathy. The pathophysiological mechanism by which the myopathy occurs has not been elucidated until now. Here we describe a patient who carries the new variant of ANXA11 p.Asp40Ile and shows a severe and rapidly progressive childhood-onset oculopharyngeal muscular dystrophy, mainly characterized by ptosis, ophthalmopl...
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: D. Natera-de Benito, J. Olival, C. Garcia-Cabau, A. Codina, M. Roldan, J. Exp ósito-Escudero, C. Batlle, L. Carrera-García, C. Ortez, C. Jou, X. Salvatella, F. Palau, A. Nascimento, J. Hoenicka Source Type: research
P.151 - ABSTRACT WITHDRAWN Myopathy caused by mutations in the HNRNPA1 gene
We previously described an adult-onset distal myopathy (MPD3, OMIM #610099) in a large Finnish family with a dominant mode of inheritance. Small hand muscles (intrinsic, thenar and hypothenar) were first involved with spread to the lower legs and later proximal muscles. Dystrophic changes with rimmed vacuoles and cytoplasmic inclusions were observed in muscle biopsies at advanced stage. The causative variant was identified in the HNRNPA1 gene. This was a heterozygous deletion of the DNA segment chr12:54677979-54678138 spanning the second last exon 10 of the gene.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: P. Hackman, S. V älipakka, P. Jonson, J. Sarparanta, A. Vihola, M. Johari, M. Savarese, B. Udd Source Type: research
FP.32 BAG3 p.P209L variant leads to changes in nuclear and actomyosin dynamics and impairment of the transmission of mechanical signals
The transmission of mechanical signals throughout the cell is important for cell function and cell fate decisions, turning mechanical tension into dynamic responses. This is achieved through the coupling of the nucleus and cytoskeleton via the LINC complex. While BAG3 myofibrillar myopathy, caused by the Pro209Leu variant, is typically thought of as a disease which primarily affects the Z-disk, here we show evidence of a role for BAG3 in mechanotransduction. Our mPro215Leu knock-in/knock-out mouse model, as well as patient derived fibroblasts, show an increase in nuclear abnormalities.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: R. Robertson, M. Dicaire, J. Lavoie, B. Brais Source Type: research
VP.48 Clinicopathological characteristics of 105 patients with idiopathic inflammatory myopathy based on muscle specific antibodies
In this study, we aimed to analyze the clinicopathological features and treatment outcome of IIM patients. We analyzed clinical and pathological findings of IIM patients, who underwent muscle biopsy from January 2008 to December 2020. We excluded inclusion body myositis cases. We enrolled 105 IIM patients. Male to female ratio was 31:74 and the average age was 60.8 years old.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: A. Yamanaka, N. Eura, T. Shiota, M. Yamaoka, Y. Nishimori, N. Iguchi, M. Ozaki, H. Nanaura, N. Iwasa, T. Kiriyama, T. Izumi, H. Kataoka, K. Sugie Source Type: research
P.178 Clinical classification of variants in the valosin containing protein gene associated with multisystem proteinopathy
This study reports novel VCP variants and evaluates evidence to assess their pathogenicity. Novel and/or non-previously clinically characterized variants in the VCP gene were identified in the VCP International Multicentre Study, a retrospective descriptive study which collected clinical, genetic and ancillary test data from 255 patients with VCP.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: J. D íaz Manera, M. Schiava, C. Ikenaga, T. Stojkovic, I. Nishino, S. Nair, G. Manousakis, C. Quinn, Z. Sahenk, M. Monforte, A. Oldfors, E. Pal, B. Velez Gomez, J. de Bleecker, M. Farrugia, M. Harms, S. Ralston, J. Sotoca Fernandez, J. Bevilacqua Source Type: research
P.174 TRIM32 related muscular dystrophy mimicking inflammatory myopathy: Clinical and histopathological features in two siblings
Mutations in TRIM32 are associated with limb-girdle muscular dystrophy R8, also known as sarcotubular myopathy (OMIM#254110). Here we present two siblings who are compound heterozygotes for a deletion of the entire coding sequence, and a missense pathogenic variant c.1459G>A (pAsp487Asn). The first patient is a woman who developed myalgias and hyperCkemia in her thirties, followed by slowly progressive mild lower extremity weakness, while remaining ambulatory without assistance at the age of 60 years.
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: R. Orbach, L. Ostrow, R. Roda Source Type: research
