The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Ikuya Nonaka - One of the best experts on this subject based on the ideXlab platform.
-
Distal Myopathy in multi-minicore disease.
Internal Medicine, 2009Co-Authors: Satomi Mitsuhashi, Ikuya Nonaka, Shiwen Wu, Carlos Alberto Ibarra Moreno, S. Shalaby, Yukiko K. Hayashi, Satoru Noguchi, Ichizo NishinoAbstract:A 52-year-old man noted Distal dominant slowly progressive muscle weakness at age 36 years. On muscle CT, the red muscles of the soleus, anterior tibial and paraspinal muscles, where type 1 fiber is known to predominate, were almost totally replaced by fat tissue while quadriceps femoris, gastrocnemius and upper extremity muscles were relatively spared. Quadriceps muscle biopsy revealed multi-minicores in addition to occasional larger cores, in about 70% of the type 1 fibers. A novel heterozygous nucleotide change c.5869T > A (p.S1957T) was identified in RYR1. Although pathogenicity was not confirmed, this nucleotide change was absent in 100 control DNA. We did not find a mutation in either multi-minicore disease-associated gene, SEPN1, or major Distal Myopathy-related genes, including GNE, ZASP, MYOT, exons 32-36 of MYH7, and the last exon of TTN. This is probably a unique form of Distal Myopathy characterized by the presence of multi-minicores with preferential involvement of type 1 fibers.
-
Distal Myopathy with rimmed vacuoles and hereditary inclusion body Myopathy
Current Neurology and Neuroscience Reports, 2005Co-Authors: Ikuya Nonaka, S Noguchi, Ichizo NishinoAbstract:Distal Myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body Myopathy (hIBM) share similar clinical features, including onset in young adulthood with preferential involvement of the anterior compartment of the lower legs and sparing of the quadriceps femoris muscles. The most significant muscle pathology is the presence of rimmed vacuoles, which appear to play a major role in muscle atrophy and weakness. After the discovery of the gene locus in both DMRV and hIBM on chromosome 9 and mutations in the gene encoding the enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), it became clear that they are allelic disorders. From gene analysis, it is evident that these diseases are not restricted to people of Japanese and Jewish ancestry, but that they are widely distributed throughout all ethnic groups. Although defective glycosylation to a muscle fiber has been suggested, the mechanism by which myofibrillar degeneration is followed by rimmed vacuole formation remains to be clarified.
-
reduction of udp n acetylglucosamine 2 epimerase n acetylmannosamine kinase activity and sialylation in Distal Myopathy with rimmed vacuoles
Journal of Biological Chemistry, 2004Co-Authors: S Noguchi, Yukiko K. Hayashi, Kumiko Murayama, Yoko Keira, Megumu Ogawa, Masako Fujita, Genri Kawahara, Masaoki Imazawa, Yuichi Goto, Ikuya NonakaAbstract:Abstract Distal Myopathy with rimmed vacuoles is an autosomal recessive muscle disease with preferential involvement of the tibialis anterior that spares the quadriceps muscles in young adulthood. In a Japanese patient with Distal Myopathy with rimmed vacuoles, we identified pathogenic mutations in the gene encoding the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, which catalyzes the initial two steps in the biosynthesis of sialic acid. In this study, we demonstrated the relationship between the genetic mutations and enzymatic activities using an in vitro expression assay system. Furthermore, we also showed that the levels of sialic acid in muscle and primary cultured cells from DMRV patients were reduced to 60–75% of control. The reactivities to lectins were also variable in some myofibers, suggesting that hyposialylation and abnormal glycosylation in muscles may contribute to the focal accumulations of autophagic vacuoles, amyloid deposits, or both in patient muscle tissue. The addition of ManNAc and NeuAc to primary cultured cells normalized sialylation levels, thus demonstrating the therapeutic potential of these compounds for this disease.
-
apoptotic muscle fiber degeneration in Distal Myopathy with rimmed vacuoles
Acta Neuropathologica, 2001Co-Authors: Koji Ikezoe, Ikuya NonakaAbstract:Rimmed vacuole formation, tubulofilamentous nuclear inclusions and muscle fiber atrophy are the characteristic pathological findings in Distal Myopathy with rimmed vacuoles (DMRV). Necrotic muscle fibers were few in number and did not appear to account for the muscle weakness, but the nuclear changes with myofibrillar degeneration followed by rimmed vacuole formation appeared to be the major reason for the muscle fiber atrophy in DMRV. To determine whether the nuclear change in DMRV was related to apoptosis, we examined 15 muscle biopsy specimens immunohistochemically, and 7 of them ultrastructurally. The characteristic tubulofilamentous nuclear inclusions were found in 4 and the typical fragmented apoptotic nuclei in 3 of the 7 muscle biopsy samples examined by electron microscopy. TUNEL-positive nuclei reflecting apoptotic DNA fragmentation were found in 13 of 15 biopsies ranging from a few to approximately 1.5% of myonuclei. Apoptosis-specific protein was expressed in the sarcoplasm of atrophic fibers in 13 biopsies both with or without rimmed vacuoles. These findings suggest that the apoptotic process plays a crucial role in myofibrillar degeneration followed by autophagocytosis, i.e., rimmed vacuole formation, in DMRV.
-
Distal Myopathy with rimmed vacuoles
Neuromuscular Disorders, 1998Co-Authors: Ikuya Nonaka, Nobuyuki Murakami, Y Suzuki, Mitsuru KawaiAbstract:Abstract Distal Myopathy with rimmed vacuoles is an autosomal recessively inherited disorder with preferential involvement of the anterior tibial muscle. Recently the gene was discovered to be mapped to chromosome 9, the same region as in familial inclusion body Myopathy (rimmed vacuole Myopathy sparing the quadriceps). The onset of the disease was in young adults 20–40 years of age, averaging 26 years. The disease was progressive and most of the patients became non-ambulant within 12 years after the onset. The striking and common pathologic finding was the presence of rimmed vacuoles in muscle fibers with little evidence of necrotic or regenerative processes. Nuclear change with tubulofilamentous inclusions probably induces focal myofibrillar degeneration which activates the lysosomal system, resulting in active autophagocytosis and myelin body formation, i.e. rimmed vacuole formation.
Peter Hackman - One of the best experts on this subject based on the ideXlab platform.
-
Distal Myopathy caused by homozygous missense mutations in the nebulin gene. Commentary
Brain, 2020Co-Authors: Carina Wallgren-pettersson, Vilma-lotta Lehtokari, Katarina Pelin, Anders Paetau, Peter Hackman, Hannu Kalimo, Elina Nuutinen, C Sewry, Nigel LaingAbstract:We describe a novel, recessively inherited Distal Myopathy caused by homozygous missense mutations in the nebulin gene (NEB), in which other combinations of mutations are known to cause nemaline (rod) Myopathy (NM).Two different missense mutations were identified in homozygous form in seven Finnish patients from four unrelated families with childhood or adult-onset foot drop. Both mutations, when combined in compound heterozygous form with more disruptive mutations in NEB, are known to cause NM. Hitherto, no patients with NM have been found to have two missense mutations in NEB. Muscle weakness predominantly affected ankle dorsiflexors, finger extensors and neck flexors, a distribution different both from the patterns of weakness seen in NM caused by NEB mutations, and those of the known recessively inherited Distal myopathies. Singleton cases need to be distinguished from the Laing type of Distal Myopathy. Histologically, this Myopathy differs from NM in that nemaline bodies were not detectable with routine light microscopy, and they were inconspicuous or absent even with electron microscopy. Rimmed vacuoles, commonly seen in other Distal myopathies, were not a feature. We conclude that homozygous missense mutations in NEB cause a novel Distal Myopathy, predominantly involving lower leg extensor muscles, finger extensors and neck flexors.
-
sqstm1 splice site mutation in Distal Myopathy with rimmed vacuoles
Neurology, 2015Co-Authors: Robert C Bucelli, Khalid Arhzaouy, Alan Pestronk, Sara K Pittman, Luisa Rojas, Anni Evila, Peter Hackman, Matthew B Harms, Conrad C WeihlAbstract:Objective: To identify the genetic etiology and characterize the clinicopathologic features of a novel Distal Myopathy. Methods: We performed whole-exome sequencing on a family with an autosomal dominant Distal Myopathy and targeted exome sequencing in 1 patient with sporadic Distal Myopathy, both with rimmed vacuolar pathology. We also evaluated the pathogenicity of identified mutations using immunohistochemistry, Western blot analysis, and expression studies. Results: Sequencing identified a likely pathogenic c.1165+1 G>A splice donor variant in SQSTM1 in the affected members of 1 family and in an unrelated patient with sporadic Distal Myopathy. Affected patients had late-onset Distal lower extremity weakness, myopathic features on EMG, and muscle pathology demonstrating rimmed vacuoles with both TAR DNA-binding protein 43 and SQSTM1 inclusions. The c.1165+1 G>A SQSTM1 variant results in the expression of 2 alternatively spliced SQSTM1 proteins: 1 lacking the C-terminal PEST2 domain and another lacking the C-terminal ubiquitin-associated (UBA) domain, both of which have distinct patterns of cellular and skeletal muscle localization. Conclusions: SQSTM1 is an autophagic adaptor that shuttles aggregated and ubiquitinated proteins to the autophagosome for degradation via its C-terminal UBA domain. Similar to mutations in VCP, dominantly inherited mutations in SQSTM1 are now associated with rimmed vacuolar Myopathy, Paget disease of bone, amyotrophic lateral sclerosis, and frontotemporal dementia. Our data further suggest a pathogenic connection between the disparate phenotypes.
-
welander Distal Myopathy is caused by a mutation in the rna binding protein tia1
Annals of Neurology, 2013Co-Authors: Peter Hackman, Anni Evila, J. Sarparanta, Sara Lehtinen, Per Harald Jonson, H. Luque, Anna Vihola, Juha Kere, Mark ScreenAbstract:Objective A study was undertaken to identify the molecular cause of Welander Distal Myopathy (WDM), a classic autosomal dominant Distal Myopathy. Methods The genetic linkage was confirmed and defined by microsatellite and single nucleotide polymorphism haplotyping. The whole linked genomic region was sequenced with targeted high-throughput and Sanger sequencing, and coding transcripts were sequenced on the cDNA level. WDM muscle biopsies were studied by Western blotting and immunofluorescence microscopy. Splicing of TIA1 and its target genes in muscle and myoblast cultures was analyzed by reverse transcriptase polymerase chain reaction. Mutant TIA1 was characterized by cell biological studies on HeLa cells, including quantification of stress granules by high content analysis and fluorescence recovery after photobleaching (FRAP) experiments. Results The linked haplotype at 2p13 was narrowed down to A (p.E384K) in the RNA-binding protein TIA1, a key component of stress granules. Immunofluorescence microscopy of WDM biopsies showed a focal increase of TIA1 in atrophic and vacuolated fibers. In HeLa cells, mutant TIA1 constructs caused a mild increase in stress granule abundance compared to wild type, and showed slower average fluorescence recovery in FRAP. Interpretation WDM is caused by mutated TIA1 through a dominant pathomechanism probably involving altered stress granule dynamics. Ann Neurol 2013;73:500–509
-
G.O.1 Welander Distal Myopathy is caused by a mutated RNA binding protein
Neuromuscular Disorders, 2012Co-Authors: Peter Hackman, Anni Evila, J. Sarparanta, Sara Lehtinen, A. Naukkarinen, Per Harald Jonson, H. Luque, Mark Screen, Lars EdströmAbstract:Abstract Welander Distal Myopathy (WDM) is a late onset, autosomal dominant Distal Myopathy prevalent in Finland and Sweden. First symptoms of finger extensor weakness occur after age 40, with progression to all hand muscles and ankle dorsiflexion. Rare homozygotes show also proximal muscular weakness, earlier onset and faster progression. WDM is linked to chromosome 2p13 with a maximal linked region of interest of
-
distinct Distal Myopathy phenotype caused by vcp gene mutation in a finnish family
Neuromuscular Disorders, 2011Co-Authors: Johanna Palmio, Sini Penttila, Peter Hackman, Satu Sandell, Tiina Suominen, Olayinka Raheem, Sanna Huovinen, Hannu HaapasaloAbstract:Abstract Inclusion body Myopathy with Paget disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin-containing protein (VCP) gene. We report a new Distal phenotype caused by VCP gene mutation in a Finnish family with nine affected members in three generations. Patients had onset of Distal leg muscle weakness and atrophy in the anterior compartment muscles after age 35, which caused a foot drop at age 50. None of the siblings had scapular winging, proximal Myopathy, cardioMyopathy or respiratory problems during long-term follow-up. Three Distal Myopathy patients developed rapidly progressive dementia, became bedridden and died of cachexia and pneumonia and VCP gene mutation P137L (c.410C>T) was then identified in the family. Late onset autosomal dominant Distal Myopathy with rimmed vacuolar muscle pathology was not sufficient for exact diagnosis in this family until late-occurring dementia provided the clue for molecular diagnosis. VCP needs to be considered in the differential diagnostic work-up in patients with Distal Myopathy phenotype.
Nobuyuki Murakami - One of the best experts on this subject based on the ideXlab platform.
-
Distal Myopathy with rimmed vacuoles
Neuromuscular Disorders, 1998Co-Authors: Ikuya Nonaka, Nobuyuki Murakami, Y Suzuki, Mitsuru KawaiAbstract:Abstract Distal Myopathy with rimmed vacuoles is an autosomal recessively inherited disorder with preferential involvement of the anterior tibial muscle. Recently the gene was discovered to be mapped to chromosome 9, the same region as in familial inclusion body Myopathy (rimmed vacuole Myopathy sparing the quadriceps). The onset of the disease was in young adults 20–40 years of age, averaging 26 years. The disease was progressive and most of the patients became non-ambulant within 12 years after the onset. The striking and common pathologic finding was the presence of rimmed vacuoles in muscle fibers with little evidence of necrotic or regenerative processes. Nuclear change with tubulofilamentous inclusions probably induces focal myofibrillar degeneration which activates the lysosomal system, resulting in active autophagocytosis and myelin body formation, i.e. rimmed vacuole formation.
-
Reducing bodies in Distal Myopathy with rimmed vacuole formation
Acta Neuropathologica, 1995Co-Authors: Beatriz H. Kiyomoto, Nobuhiko Sunohara, Nobuyuki Murakami, Jun Kishibayashi, Ikuya NonakaAbstract:A 42-year-old woman with Distal Myopathy with rimmed vacuoles had intracytoplasmic inclusion bodies similar to those described in reducing body Myopathy. Since these inclusions were found in fibers with high acid phosphatase activity and occasional rimmed vacuoles, their formation appeared to correlate with active myofibrillar degeneration, but their origin remains unknown.
-
muscle fiber degeneration in Distal Myopathy with rimmed vacuole formation
Acta Neuropathologica, 1995Co-Authors: Nobuyuki Murakami, Yasuo Ihara, Ikuya NonakaAbstract:In 11 patients with Distal Myopathy with rimmed vacuole formation (DMRV), a well-known autosomal recessively inherited disorder, the rimmed vacuole formation appears to be the main pathological change accounting for the progressive muscle fiber degeneration. To gain a better understanding of the pathophysiology of the vacuole formation, we applied Congo red and immunohistochemical stains to muscle biopsies from these patients and the results were compared with those of patients with inclusion body myositis (IBM). The vacuoles in DMRV contained Congophilic amyloid material and deposits immunoreactive for β-amyloid protein, both the NH2 and COOH termini of β-amyloid protein precursor, ubiquitin, and tau protein. These results were similar to those seen in our present cases of IBM as well as in previously reported cases. Therefore, there may be no pathogenetic differences in the formation of rimmed vacuoles in DMRV and IBM. Nevertheless, the degenerative process involved in rimmed vacuole formation in various diseases may share a common pathogenetic mechanism with that in amyloid-plaque formation in Alzheimer's disease brain as has been proposed previously.
Nigel G Laing - One of the best experts on this subject based on the ideXlab platform.
-
cystinosis Distal Myopathy novel clinical pathological and genetic features
Neuromuscular Disorders, 2017Co-Authors: Nigel G Laing, Alan Pestronk, Conrad C Weihl, Macarena Cabreraserrano, Reimar Junckerstorff, Ali Alisheri, P J LamontAbstract:Abstract Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues. Some patients develop a Distal Myopathy involving mainly hand muscles. Myopathology descriptions from only 5 patients are available in the literature. We present a comprehensive clinical, pathological and genetic description of 3 patients from 2 families with nephropathic cystinosis. Intrafamiliar variability was detected in one family in which one sibling developed a severe Distal Myopathy while the other sibling did not show any signs of skeletal muscle involvement. One of the patients was on treatment with Cysteamine for over 12 years but still developed the usual complications of nephropathic cystinosis in his twenties. Novel pathological findings consisting in sarcoplasmic deposits reactive for slow myosin were identified. Three previously known and one novel mutation are reported. Nephropathic cystinosis should be included in the differential diagnosis of Distal myopathies in those with early renal failure. Novel clinical and pathological features are reported here contributing to the characterization of the muscle involvement in nephropathic cystinosis.
-
complex sarcolemmal invaginations mimicking myotendinous junctions in a case of laing early onset Distal Myopathy
Neuropathology, 2015Co-Authors: Gerald F Reis, Nigel G Laing, G De La Motte, Rebecca Gooding, Marta MargetaAbstract:Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset Distal Myopathy (MPD1) is a form of Distal Myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis.
-
p 3 9 unusual pathologic features in a patient with clinical features of laing early onset Distal Myopathy
Neuromuscular Disorders, 2013Co-Authors: Marta Margeta, G De La Motte, Nigel G LaingAbstract:Laing early onset Distal Myopathy (MPD1) is a rare form of Distal Myopathy caused by mutations in myosin heavy gene MHY7. While clinical presentation of MPD1 patients is fairly stereotypical (development of complete bilateral foot drop in the early childhood, followed by a very slow or no clinical progression in subsequent years), the biopsy findings are relatively nonspecific except for the lack of rimmed vacuoles (which are a common feature of Distal myopathies). Here, we present a patient with clinical features of MPD1 but distinctive light microscopic and ultrastructural findings on muscle biopsy. The patient, a 39 year old male, developed bilateral foot drop at age 5, but is otherwise asymptomatic and physically active. Physical exam showed bilateral weakness of ankle dorsiflexors (1/5), toe extensors (1/5), and finger extensors (4+/5); creatine kinase level was within the normal limits. The disease first developed in the patient’s paternal grandmother and is transmitted in autosomal dominant fashion, with all affected family members showing the same clinical phenotype. The vastus lateralis biopsy showed mild-moderate variation in fiber diameters, mild fibrosis, scattered nuclear clumps, and type 1 fiber predominance (85%), but no rimmed vacuoles; rare fibers contained cytoplasmic or subsarcolemmal desmin-positive inclusions. In addition, scattered type 1 (but no type 2) fibers had unusual, partially septated/lobulated appearance. On ultrastructural analysis, these septations corresponded to complex invaginations of the plasma membrane that were somewhat reminiscent of myotendinous junctions but randomly distributed throughout the biopsy. Genetic analysis, currently in progress, will show whether these unusual histologic and ultrastructural features widen the pathologic spectrum of MPD1 or define a genetically distinct type of MPD1-like Distal Myopathy.
-
laing early onset Distal Myopathy slow myosin defect with variable abnormalities on muscle biopsy
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: P J Lamont, F L Mastaglia, T Voit, Marianne De Visser, Peter Hedera, Leslie R Bridges, V Fabian, Annemieke Rozemuller, Nigel G LaingAbstract:Background: Laing early onset Distal Myopathy (MPD1) is an autosomal dominant Myopathy caused by mutations within the slow skeletal muscle fibre myosin heavy chain gene, MYH7. It is allelic with myosin storage Myopathy, with the commonest form of familial hypertrophic cardioMyopathy, and with one form of dilated cardioMyopathy. However, the clinical picture of MPD1 is distinct from these three conditions. Objective: To collate and discuss the histological features reported in the muscle biopsies of MPD1 patients and to outline the clinical features. Results: The phenotype of MPD1 was consistent, with initial weakness of great toe/ankle dorsiflexion, and later development of weakness of finger extension and neck flexion. Age of onset was the only variable, being from birth up to the 20s, but progression was always very slow. The pathological features were variable. In this retrospective series, there were no pathognomonic diagnostic features, although atrophic type I fibres were found in half the families. Rimmed vacuoles are consistently seen in all other Distal myopathies with the exception of Myoshi Distal Myopathy. However, they were found in a minority of patients with MPD1, and were not prominent when present. Immunohistochemical staining for slow and fast myosin showed co-expression of slow and fast myosin in some type I fibres, possibly indicating a switch to type II status. This may be a useful aid to diagnosis. Conclusions: The pathological findings in MPD1 are variable and appear to be affected by factors such as the specific muscle biopsied, the age of the patient at biopsy, and the duration of disease manifestations.
-
a new dominant Distal Myopathy affecting posterior leg and anterior upper limb muscles
Neurology, 2005Co-Authors: D R Williams, Nigel G Laing, Katrina Reardon, Leslie Roberts, X Dennet, R Duff, Edward ByrneAbstract:Objective: To report a dominant, slowly progressive early onset Distal Myopathy with sparing of the tibialis anterior. Methods: Twelve affected and two possibly affected members from an Australian kindred were examined and investigated by EMG, imaging studies, histopathology, and genetic analysis. Results: Affected patients had a slowly progressive condition with symmetric, Distal weakness and wasting of the anterior upper and posterior lower limbs, with sparing of tibialis anterior, even in advanced disease. All patients remained ambulant and there was no evidence of cardiac or respiratory muscle involvement. Serum creatine kinase levels were either normal or mildly elevated. Imaging studies showed widespread involvement of the posterior and lateral leg compartments. Proximal muscles were radiologically abnormal only in advanced disease. Muscles that were mildly affected clinically appeared normal on imaging. EMG in nine patients showed widespread myopathic changes. Muscle histopathology in four patients showed either end stage muscle or nonspecific myopathic findings without inflammation or vacuoles. Microsatellite markers for Distal Myopathy loci were analyzed and all known Distal Myopathy phenotype genes and linkage regions were formally excluded by multipoint analysis. Conclusions: The affected patients in this kindred display a clinically distinct Myopathy, with selective involvement of posterior lower and anterior upper limb muscles. The genetic analysis suggests the existence of one more Distal Myopathy locus.
F. M. S. Tomé - One of the best experts on this subject based on the ideXlab platform.
-
autosomal recessive oculopharyngoDistal Myopathy in light of Distal Myopathy with rimmed vacuoles and oculopharyngeal muscular dystrophy
Neuromuscular Disorders, 1998Co-Authors: Eiichiro Uyama, Makoto Uchino, Danielle Chateau, F. M. S. ToméAbstract:Abstract We investigated two Japanese siblings presenting with oculopharyngoDistal Myopathy, whose healthy parents were consanguineous. To clarify their disease characteristics, we compared them with four patients with Distal Myopathy with rimmed vacuoles linked to chromosome 9p1-q1, and 36 patients with oculopharyngeal muscular dystrophy linked to 14q11.2-q13. The first symptom in the patients with autosomal recessive oculopharyngoDistal Myopathy was weakness of the tibialis anterior muscle. Their biceps muscles showed initial and advanced myogenic changes, with rimmed vacuoles in 3% and 6% of the muscle fibers, respectively. In contrast, patients with Distal Myopathy with rimmed vacuoles revealed many rimmed vacuoles, on average in 20% of the fibers, and their oculopharyngeal muscles were spared. None of the patients with oculopharyngeal muscular dystrophy showed Distal dominant weakness and the occurrence of rimmed vacuoles was rare. Ultrastructural studies in groups of autosomal recessive oculopharyngoDistal Myopathy and Distal Myopathy with rimmed vacuoles disclosed a collection of cytoplasmic filaments of 16–18 nm, but oculopharyngeal muscular dystrophy-specific intranuclear inclusions of 8.5 nm were not found. Thus, the phenotype of autosomal recessive oculopharyngoDistal Myopathy is distinct from Distal Myopathy with rimmed vacuoles and oculopharyngeal muscular dystrophy, but shares some ultrastructural characteristics with Distal Myopathy with rimmed vacuoles and hereditary inclusion body Myopathy.
-
Intranuclear and cytoplasmic filamentous inclusions in Distal Myopathy (Welander)
Acta Neuropathologica, 1991Co-Authors: K. Borg, F. M. S. Tomé, L. EdströmAbstract:Ultrastructural examination of anterior tibial muscle from four patients with late-onset autosomal dominant Distal Myopathy of Welander-type revealed intrasarcoplasmic filamentous inclusions in association with rimmed vacuoles. In one of the patients, identical intranuclear filamentous inclusions were also found. These filamentous inclusions are similar to those desxribed in inclusion body myositis (IBM). They have also been observed in hereditary neuromuscular disorders including autosomal recessive Distal Myopathy. Thus, the filamentous inclusions occur in different neuromuscular conditions with different etiologies. These findings further raise the question of the specificity of the filamentous inclusions in IBM.