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S. Blumen - One of the best experts on this subject based on the ideXlab platform.
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PABPN1 gene therapy for Oculopharyngeal Muscular Dystrophy
Nature Communications, 2017Co-Authors: A. Malerba, P. Klein, H. Bachtarzi, S Jarmin, G. Cordova, A. Ferry, V. Strings, M Polay Espinoza, K. Mamchaoui, S. BlumenAbstract:Oculopharyngeal Muscular Dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment.
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Cognitive impairment and reduced life span of Oculopharyngeal Muscular Dystrophy homozygotes.
Neurology, 2009Co-Authors: S. Blumen, Bernard Brais, Jean-pierre Bouchard, R.l. Carasso, D. Paleacu, Vivian E. Drory, S. Chantal, N. Blumen, I. BravermanAbstract:Objective: To assess the evolution and life expectancy in patients with Oculopharyngeal Muscular Dystrophy (OPMD) who are homozygotes for two (GCN)13 expansions in the PABPN1 encoding gene. Background: OPMD is particularly frequent among French Canadians (FCs) and Uzbek Jews (UJs), who carry a same size, (GCN)13, PABPN1 mutation. The high rate of consanguinity among UJs together with late disease onset and normal fertility results in homozygous cases. Methods: For 15 to 20 years, we followed 4 FC and 6 UJ homozygotes with OPMD and compared them with their heterozygous parents and siblings. In addition to clinical evaluation, electrodiagnostic tests, psychological tests, and brain imaging studies were performed. Results: In all (GCN)13–(GCN)13 patients, OPMD started before age 35 years, with bilateral ptosis and dysphagia; external ophthalmoparesis and dysphonia followed within a few years, as well as weakness in proximal limb muscles. All patients had recurrent aspirations and lost weight; 4 patients required surgical interventions to alleviate dysphagia, and 5 required feeding gastrostomies. Most patients were followed by psychiatrists due to cognitive decline, recurrent depression, or psychotic episodes. Six patients died at ages 50, 51, 53, 56, 56, and 57 years. The eldest patient is now 51 years old; she is cachectic and requires special diet and psychiatric care for paranoid psychosis and uninhibited behavior. Conclusions: Oculopharyngeal Muscular Dystrophy progresses faster in homozygote compared with heterozygote patients. It is not restricted to the muscles, but also involves the CNS with cognitive decline and psychotic manifestations and leads to a reduced life expectancy.
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Homozygotes for Oculopharyngeal Muscular Dystrophy have a severe form of the disease
Annals of neurology, 1999Co-Authors: S. Blumen, Bernard Brais, Jean-pierre Bouchard, François Codère, Amos D. Korczyn, Susan Medinsky, Joab Chapman, A. Asherov, P. Nisipeanu, M. FardeauAbstract:Autosomal dominant Oculopharyngeal Muscular Dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%). Ann Neurol 1999;46:115–118
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Epidemiology and inheritance of Oculopharyngeal Muscular Dystrophy in Israel
Neuromuscular Disorders, 1997Co-Authors: S. Blumen, Menachem Sadeh, A. Asherov, P. Nisipeanu, R.l. Carasso, N. Blumen, Y. Wirguin, O. Khilkevich, Amos D. KorczynAbstract:Abstract Oculopharyngeal Muscular Dystrophy (OPMD) is considered frequent among French Canadians. Our previous observations suggested it is common also among the Jews originating from Bukhara in Uzbekistan, many of whom are now living in Israel. One hundred and seventeen OPMD patients were identified in a population of 70 000 people of Bukharian descent, resulting in a calculated minimal prevalence of 1:600. In all but three families age dependent autosomal dominant inheritance was documented. There is some evidence for genetic anticipation. Three young, severely ill, patients from two different families may be homozygotes, their parents being both affected. Bukhara Jews present the second largest known cluster and the prevalence is the highest in the world. The existence of very large families, intermarriage among carriers and probably homozygote offspring may be useful for genetic studies. A ‘founder effect’ may explain the high prevalence of OPMD in this population.
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Intranuclear inclusions in Oculopharyngeal Muscular Dystrophy among Bukhara Jews
Neurology, 1996Co-Authors: S. Blumen, Menachem Sadeh, Amos D. Korczyn, A. Asherov, P. Nisipeanu, A. Rouche, Fernando M.s. ToméAbstract:We studied, by electron microscopy, muscle biopsies from seven patients with autosomal dominant Oculopharyngeal Muscular Dystrophy (OPMD) belonging to the recently described Bukhara-Jewish cluster. Typical tubulofilamentous intranuclear inclusions (INI) of 8.5 nm outer diameter were present in all cases. The IN1 were observed in 4.5 ± 1.8% of the nuclei in five patients. In the other two, they occurred in 9.5 ± 0.5% of the nuclei and often occupied a larger nuclear area. These two patients, offspring of intermarriage between affected cousins, had an unusually severe form of OPMD beginning in their early 30s, suggesting homozygote state. Our results confirm that IN1 are pathognomonic for OPMD and suggest that their frequency may be quantitatively related to the number of abnormal DNA copies.
Bernard Brais - One of the best experts on this subject based on the ideXlab platform.
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A study of impairments in Oculopharyngeal Muscular Dystrophy.
Muscle & nerve, 2020Co-Authors: Jean-denis Brisson, Bernard Brais, Cynthia Gagnon, Isabelle Côté, Jean MathieuAbstract:Introduction In this study we aimed to document the prevalence and age of onset of motor impairments and other key symptoms in Oculopharyngeal Muscular Dystrophy (OPMD). Methods Retrospective chart review of patients followed at the Saguenay NeuroMuscular Clinic (Quebec, Canada). Results A total of 333 participants with the (GCN)13 mutation were included. Before the age of 75 years, 27% of them had walking limitations, 14% could not climb stairs independently, and 14% used a wheelchair for long distances or daily living. The median age of onset was 54 years for ptosis and dysphagia and 58 years for lower limb proximal weakness. Other frequent symptoms included fatigue, pharyngeal pooling of thickened secretions, and dysphonia. The median age at death was 77 years and the main cause was respiratory disease. Discussion This study provides important information to help anticipatory guidance for affected people and for the development of therapeutic trials in OPMD.
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Oculopharyngeal Muscular Dystrophy.
Handbook of clinical neurology, 2011Co-Authors: Bernard BraisAbstract:Publisher Summary Oculopharyngeal Muscular Dystrophy (OPMD) is a late-onset muscle disease associated with progressive ptosis of the eyelids, dysphagia, and unique tubulofilamentous intranuclear inclusions (INIs) in skeletal muscle. OPMD is usually transmitted as an autosomal dominant trait and a rarer allelic autosomal recessive form has also been observed. Both forms are caused by short (GCN)11–17 expansions in the polyadenylate-binding protein nuclear 1 gene (PABPN1), localized on chromosome 14q11.2. OPMD usually manifests itself in the fifth or sixth decade by eyelid ptosis and dysphagia. Later, all extraocular and other voluntary muscles may become affected. In advanced stages of the disease, the eyelids become very thin and transparent. The forehead is permanently wrinkled, the eyebrows are raised, and the supraorbital ridges appear prominent. Initially, OPMD is often restricted to the levator palpebrae and pharyngeal muscles. As the disease progresses, there may be impairment of extraocular movements, occasionally associated with diplopia; nevertheless, complete external ophthalmoplegia is infrequent. Involvement of the orbicularis oculi may also occur. The intrinsic eye muscles are always spared and retinal function is not affected. The dysphagia is noticed first for solid foods and progresses insidiously.
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Cognitive impairment and reduced life span of Oculopharyngeal Muscular Dystrophy homozygotes.
Neurology, 2009Co-Authors: S. Blumen, Bernard Brais, Jean-pierre Bouchard, R.l. Carasso, D. Paleacu, Vivian E. Drory, S. Chantal, N. Blumen, I. BravermanAbstract:Objective: To assess the evolution and life expectancy in patients with Oculopharyngeal Muscular Dystrophy (OPMD) who are homozygotes for two (GCN)13 expansions in the PABPN1 encoding gene. Background: OPMD is particularly frequent among French Canadians (FCs) and Uzbek Jews (UJs), who carry a same size, (GCN)13, PABPN1 mutation. The high rate of consanguinity among UJs together with late disease onset and normal fertility results in homozygous cases. Methods: For 15 to 20 years, we followed 4 FC and 6 UJ homozygotes with OPMD and compared them with their heterozygous parents and siblings. In addition to clinical evaluation, electrodiagnostic tests, psychological tests, and brain imaging studies were performed. Results: In all (GCN)13–(GCN)13 patients, OPMD started before age 35 years, with bilateral ptosis and dysphagia; external ophthalmoparesis and dysphonia followed within a few years, as well as weakness in proximal limb muscles. All patients had recurrent aspirations and lost weight; 4 patients required surgical interventions to alleviate dysphagia, and 5 required feeding gastrostomies. Most patients were followed by psychiatrists due to cognitive decline, recurrent depression, or psychotic episodes. Six patients died at ages 50, 51, 53, 56, 56, and 57 years. The eldest patient is now 51 years old; she is cachectic and requires special diet and psychiatric care for paranoid psychosis and uninhibited behavior. Conclusions: Oculopharyngeal Muscular Dystrophy progresses faster in homozygote compared with heterozygote patients. It is not restricted to the muscles, but also involves the CNS with cognitive decline and psychotic manifestations and leads to a reduced life expectancy.
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Oculopharyngeal Muscular Dystrophy: a polyalanine myopathy.
Current neurology and neuroscience reports, 2008Co-Authors: Bernard BraisAbstract:It has been 10 years since the identification of the first PABPN1 gene (GCN)n/polyalanine mutations responsible for Oculopharyngeal Muscular Dystrophy (OPMD). These mutations have been found in most cases of OPMD diagnosed in more than 35 countries. Sequence analyses have shown that such mutations have occurred numerous times in human history. Although PABPN1 was found early on to be a component of the classic filamentous intranuclear inclusions (INIs), mRNA and other proteins also have been found to coaggregate in the INIs. It is still unclear if the INIs play a pathologic or a protective role. The generation of numerous cell and animal models of OPMD has led to greater insight into its complex molecular pathophysiology and identified the first candidate therapeutic molecules. This paper reviews basic and clinical research on OPMD, with special emphasis on recent developments in the understanding of its pathophysiology.
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Soluble expanded PABPN1 promotes cell death in Oculopharyngeal Muscular Dystrophy
Neurobiology of disease, 2007Co-Authors: Christiane Messaed, Bernard Brais, Daniel Rochefort, Janet Laganière, Patrick A. Dion, Aida Abu-baker, Guy A. RouleauAbstract:Oculopharyngeal Muscular Dystrophy (OPMD) is an autosomal dominant disease caused by the expansion of a polyalanine repeat (GCG)(8-13) in exon 1 of the PABPN1 gene. Skeletal muscle fibers nuclei from OPMD patients contain insoluble polyalanine expanded PABPN1 (expPABPN1) nuclear aggregates that sequester different cellular components. Whether these aggregates are pathogenic, or the consequence of a molecular defense mechanism, remains controversial in the field of neurodegenerative disorders and OPMD. Our cellular model shows that interfering with the formation of expPABPN1-induced large nuclear aggregates increases the availability of nuclear expPABPN1 and significantly exacerbates cell death. Live microscopy reveals that cells harboring an increased amount of the soluble forms of expPABPN1 are significantly more prone to toxicity than those with nuclear aggregates. This is the first report directly indicating that nuclear aggregation in OPMD may reflect an active process by which cells sequester and inactivate the soluble toxic form of expPABPN1.
M. Fardeau - One of the best experts on this subject based on the ideXlab platform.
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NeuroMuscular Disorders - Oculopharyngeal Muscular Dystrophy.
Seminars in neurology, 1999Co-Authors: Bernard Brais, Guy A. Rouleau, Jean-pierre Bouchard, M. Fardeau, Fernando M.s. ToméAbstract:Oculopharyngeal Muscular Dystrophy most often is an autosomal dominant Muscular Dystrophy with a distinct phenotype. It is characterized by eyelid ptosis and dysphagia. This chapter discusses the etiology, genetics, pathogenesis, clinical manifestations, management, and prognosis of this relatively rare neuroMuscular disorder.
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Oculopharyngeal Muscular Dystrophy
Seminars in Neurology, 1999Co-Authors: Bernard Brais, Guy A. Rouleau, Jean-pierre Bouchard, M. Fardeau, Fernanda M. ToméAbstract:Oculopharyngeal Muscular Dystrophy most often is an autosomal dominant Muscular Dystrophy with a distinct phenotype. It is characterized by eyelid ptosis and dysphagia. This chapter discusses the etiology, genetics, pathogenesis, clinical manifestations, management, and prognosis of this relatively rare neuroMuscular disorder.
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Homozygotes for Oculopharyngeal Muscular Dystrophy have a severe form of the disease
Annals of neurology, 1999Co-Authors: S. Blumen, Bernard Brais, Jean-pierre Bouchard, François Codère, Amos D. Korczyn, Susan Medinsky, Joab Chapman, A. Asherov, P. Nisipeanu, M. FardeauAbstract:Autosomal dominant Oculopharyngeal Muscular Dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%). Ann Neurol 1999;46:115–118
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Oculopharyngeal Muscular Dystrophy in France
Neuromuscular Disorders, 1997Co-Authors: M. Fardeau, Fernando M.s. ToméAbstract:Abstract The clinical, histopathological, ultrastructural and geographical data on 29 cases of Oculopharyngeal Muscular Dystrophy (OPMD) identified by the authors in France in briefly presented. The mean age of the patients was 53.8 ± 8.1 years. Onset symptoms were ptosis ( 14 29 ), dysphagia ( 12 29 ) and limb girdle weakness ( 3 29 ). The evolution of the disease was always progressive and followed different clinical patterns. The main histological changes in muscle biopsies were atrophic angulated fibers ( 29 29 ) and rimmed vacuoles ( 25 29 ); muscle fiber necrosis was very rare ( 1 29 ). The characteristic nuclear inclusions made of 8.5-nm filaments were observed in all cases, and found in 2–5% of the nuclei in a given ultrathin section. They are the morphological marker of the disease.
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Genealogical study of Oculopharyngeal Muscular Dystrophy in France
Neuromuscular Disorders, 1997Co-Authors: G. Brunet, Fernando M.s. Tomé, Bruno Eymard, J.m. Robert, M. FardeauAbstract:This work is based on 54 probands affected by Oculopharyngeal Muscular Dystrophy (OPMD). The muscle biopsy of all these patients showed the presence of the intranuclear inclusions, specific of this disease. The residence of the probands is concentrated in three clusters: the Paris, Marseilles and Bordeaux regions. The genealogical study was carried out on 43 probands, 10 of which did not have any ascendance in France for more than two generations. The geographic origin of the 33 patients of French descent was distributed over numerous regions, not including the Paris and Marseilles regions where many patients lived. This geographic dispersion and the rarity of common genealogies of the probands, did not suggest the existence of a recent founder effect, in contrast to what is observed in the French-Canadian community. The existence of a link between French and French-Canadian families is currently being investigated.
Fernando M.s. Tomé - One of the best experts on this subject based on the ideXlab platform.
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NeuroMuscular Disorders - Oculopharyngeal Muscular Dystrophy.
Seminars in neurology, 1999Co-Authors: Bernard Brais, Guy A. Rouleau, Jean-pierre Bouchard, M. Fardeau, Fernando M.s. ToméAbstract:Oculopharyngeal Muscular Dystrophy most often is an autosomal dominant Muscular Dystrophy with a distinct phenotype. It is characterized by eyelid ptosis and dysphagia. This chapter discusses the etiology, genetics, pathogenesis, clinical manifestations, management, and prognosis of this relatively rare neuroMuscular disorder.
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Oculopharyngeal Muscular Dystrophy in France
Neuromuscular Disorders, 1997Co-Authors: M. Fardeau, Fernando M.s. ToméAbstract:Abstract The clinical, histopathological, ultrastructural and geographical data on 29 cases of Oculopharyngeal Muscular Dystrophy (OPMD) identified by the authors in France in briefly presented. The mean age of the patients was 53.8 ± 8.1 years. Onset symptoms were ptosis ( 14 29 ), dysphagia ( 12 29 ) and limb girdle weakness ( 3 29 ). The evolution of the disease was always progressive and followed different clinical patterns. The main histological changes in muscle biopsies were atrophic angulated fibers ( 29 29 ) and rimmed vacuoles ( 25 29 ); muscle fiber necrosis was very rare ( 1 29 ). The characteristic nuclear inclusions made of 8.5-nm filaments were observed in all cases, and found in 2–5% of the nuclei in a given ultrathin section. They are the morphological marker of the disease.
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Oculopharyngeal Muscular Dystrophy in Italy
Neuromuscular Disorders, 1997Co-Authors: Giovanni Meola, Fernando M.s. Tomé, Valeria Sansone, G. Rotondo, Jean-pierre BouchardAbstract:Oculopharyngeal Muscular Dystrophy (OPMD) is an autosomal dominant myopathy particularly frequent in Quebec. The few Italian cases thus far described with bilateral ptosis, dysphagia and variable muscle weakness, show non-specific dystrophic findings on muscle biopsies by light microscopy. We describe a 70-year-old Italian woman with an adult-onset ptosis, mild dysphagia and proximal muscle weakness belonging to a family segregating OPMD according to an autosomal dominant mode of inheritance. Clinical features of four of her relatives are reviewed. Muscle biopsy studied by electron microscopy showed the typical 8.5 nm in diameter intranuclear filamentous inclusions (INI). To our knowledge, this is the first Italian report of OPMD with INI. The identification of nuclear inclusions is mandatory in order to confirm the diagnosis prior to linkage analysis.
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Oculopharyngeal Muscular Dystrophy in Japan.
Neuromuscular Disorders, 1997Co-Authors: E. Uyama, Danielle Château, Fernando M.s. Tomé, O. Nohira, Makoto Tokunaga, Masayuki Ando, M. Maki, T. Okabe, Makoto UchinoAbstract:Abstract Oculopharyngeal Muscular Dystrophy (OPMD) in the European population has been frequently diagnosed, but except for one black family, the occurrence in other ethnic groups is uncertain. We identified two unrelated OPMD Japanese families, including 34 affected individuals. Major clinical manifestations were bilateral ptosis and dysphagia starting after age 40. Histologic studies of limb muscles revealed mild myogenic changes, occasional rimmed vacuoles, and small angulated fibers. By contrast, cricopharyngeal muscle showed a marked loss of fibers and massive proliferation of connective tissue. Intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm outer diameter were observed in 2–5% of the nuclei in four different biopsied muscles. One patient with recurrent aspirations underwent successful cricopharyngeal myotomy. Aerodynamic examination was useful to evaluate velopharyngeal closure function. Our investigations revealed that OPMD is a geographically widespread disorder, and ITFI may be the specific morphologic hallmark.
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Genealogical study of Oculopharyngeal Muscular Dystrophy in France
Neuromuscular Disorders, 1997Co-Authors: G. Brunet, Fernando M.s. Tomé, Bruno Eymard, J.m. Robert, M. FardeauAbstract:This work is based on 54 probands affected by Oculopharyngeal Muscular Dystrophy (OPMD). The muscle biopsy of all these patients showed the presence of the intranuclear inclusions, specific of this disease. The residence of the probands is concentrated in three clusters: the Paris, Marseilles and Bordeaux regions. The genealogical study was carried out on 43 probands, 10 of which did not have any ascendance in France for more than two generations. The geographic origin of the 33 patients of French descent was distributed over numerous regions, not including the Paris and Marseilles regions where many patients lived. This geographic dispersion and the rarity of common genealogies of the probands, did not suggest the existence of a recent founder effect, in contrast to what is observed in the French-Canadian community. The existence of a link between French and French-Canadian families is currently being investigated.
Danielle Château - One of the best experts on this subject based on the ideXlab platform.
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autosomal recessive oculopharyngodistal myopathy in light of distal myopathy with rimmed vacuoles and Oculopharyngeal Muscular Dystrophy
Neuromuscular Disorders, 1998Co-Authors: Eiichiro Uyama, Danielle Château, Makoto Uchino, Fernanda M. 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.
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Oculopharyngeal Muscular Dystrophy in Japan.
Neuromuscular Disorders, 1997Co-Authors: E. Uyama, Danielle Château, Fernando M.s. Tomé, O. Nohira, Makoto Tokunaga, Masayuki Ando, M. Maki, T. Okabe, Makoto UchinoAbstract:Abstract Oculopharyngeal Muscular Dystrophy (OPMD) in the European population has been frequently diagnosed, but except for one black family, the occurrence in other ethnic groups is uncertain. We identified two unrelated OPMD Japanese families, including 34 affected individuals. Major clinical manifestations were bilateral ptosis and dysphagia starting after age 40. Histologic studies of limb muscles revealed mild myogenic changes, occasional rimmed vacuoles, and small angulated fibers. By contrast, cricopharyngeal muscle showed a marked loss of fibers and massive proliferation of connective tissue. Intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm outer diameter were observed in 2–5% of the nuclei in four different biopsied muscles. One patient with recurrent aspirations underwent successful cricopharyngeal myotomy. Aerodynamic examination was useful to evaluate velopharyngeal closure function. Our investigations revealed that OPMD is a geographically widespread disorder, and ITFI may be the specific morphologic hallmark.
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Morphological changes in muscle fibers in Oculopharyngeal Muscular Dystrophy
Neuromuscular Disorders, 1997Co-Authors: Fernando M.s. Tomé, Danielle Château, Anne Helbling-leclerc, M. FardeauAbstract:The study of muscle biopsies of 29 cases of Oculopharyngeal Muscular Dystrophy (OPMD) showed the two main morphological features of this disease: rimmed vacuoles (in 26 cases) and intranuclear inclusions (in all cases). These inclusions are made of 8.5 nm tubular filaments and the areas occupied by them are lighter than the surrounded nucleoplasm. This can be seen by light microscopy, facilitating the detection of the tubulo-filamentous inclusions which can only be identified with certitude by electron microscopy. In a given ultrathin section the area occupied by these inclusions varied from 2% to 5% of the nuclei. The intranuclear inclusions are the morphological marker of OPMD and their finding in a muscle biopsy allows the exact diagnosis of this disease. The origin and biochemical nature of the intranuclear inclusions is unknown.
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Oculopharyngeal Muscular Dystrophy in two unrelated Japanese families
Neurology, 1996Co-Authors: E. Uyama, Danielle Château, Makoto Uchino, O. Nohira, Makoto Tokunaga, Masayuki Ando, T. Okabe, Fernando M.s. ToméAbstract:The occurrence of Oculopharyngeal Muscular Dystrophy (OPMD) in Orientals is uncertain. We identified two unrelated Japanese families, including 30 affected individuals (14 men, 16 women, mean age 58 years) of OPMD through four generations, with complete penetrance. Their major clinical manifestations were late-onset bilateral ptosis and dysphagia. Histologic studies of slightly affected muscles reveal mild myogenic changes, occasional rimmed vacuoles, and small angulated fibers. By contrast, the severely involved cricopharyngeal muscle showed marked loss of fibers and massive proliferation of connective tissue. Ultrastructural studies of four different biopsied muscles disclosed subsarcolemmal intranuclear tubulofilamentous inclusions, identical to those of non-Japanese OPMD patients.
