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1.
T.H. Fagerlund G. Islander E. Ranklev-Twetman K. Berg M.D. Ph.D. 《Clinical genetics》1996,50(6):455-458
Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy or a pharmacogenetic trait, and is believed to be closely associated with central core disease (CCD). Data support the notion that MH susceptibility is heterogeneous, with the ryanodine receptor 1 (RYR1) locus on chromosome 19 being one locus harboring a gene that can cause MH susceptibility. The gene for CCD is believed to reside in the locus on chromosome 19. In the family presented here, a girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies conducted on available family members uncovered recombination between the MH susceptibility locus and RYR1 markers. Consequently, if one postulates that the CCD gene in this family resides in the same locus as the MH susceptibility gene, an additional CCD locus different from the RYR1 locus must also be postulated. 相似文献
2.
Monnier N Romero NB Lerale J Nivoche Y Qi D MacLennan DH Fardeau M Lunardi J 《Human molecular genetics》2000,9(18):2599-2608
Central core disease (CCD) and nemaline myopathy (NM) are congenital myopathies for which differential diagnosis is often based on the presence either of cores or rods. Missense mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in some families with CCD. Mutations in the alpha-tropomyosin and alpha-actin genes have been associated with most dominant forms of NM. Analysis of the RYR1 cDNA in a French family identified a novel Y4796C mutation that lies in the C-terminal channel-forming domain of the RyR1 protein. This mutation was linked not only to a severe and penetrant form of CCD, but also to the presence of rods in the muscle fibres and to the malignant hyperthermia susceptibility (MHS) phenotype. The Y4796C mutation was introduced into a rabbit RYR1 cDNA and expressed in HEK-293 cells. Expression of the mutant RYR1 cDNA produced channels with increased caffeine sensitivity and a significantly reduced maximal level of Ca(2+) release. Single-cell Ca(2+) analysis showed that the resting cytoplasmic level was increased by 60% in cells expressing the mutant channel. These data support the view that the rate of Ca(2+) leakage is increased in the mutant channel. The resulting chronic elevation in myoplasmic concentration is likely to be responsible for the severe expression of the disease. Haplotyping analysis indicated that the mutation arose as a neomutation in the proband. This first report of a neomutation in the RYR1 gene has strong implications for genetic linkage studies of MHS or CCD, two diseases characterized by a genetic heterogeneity. 相似文献
3.
We have examined 48 Danish families in which malignant hyperthermia reactions have occurred, with respect to three of six published mutations in the gene for the calcium release channel of sarcoplasmic reticulum (the RYR1 gene) believed to cause malignant hyperthermia susceptibility in man. The mutations are Arg614Cys, also known as the "pig mutation"; Arg163Cys; and Ile403Met. The only mutation found was Arg163Cys, which was detected in only one family. The results of this study indicate that other mutations must underlie the disorder in most Danish malignant hyperthermia-susceptible families, and that the "pig mutation" is not a frequent cause of malignant hyperthermia susceptibility in Denmark. 相似文献
4.
Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder, is mostly inherited as an autosomal dominant trait. Exposure of susceptible individuals to volatile halogenated anaesthetics can lead to a MH episode resulting in irreversible tissue damages or to the patient's death if not immediately reversed by dantrolene treatment. A MH episode is characterised by a combination of hyperthermia, skeletal muscle rigidity and hypermetabolism. Porcine stress syndrome has proved to be a valuable model for physiopathological studies of MHS. Malignant hyperthermia syndrome is associated with a failure of the calcium homeostasis in muscular fibres. Dysfunction of the calcium channels: the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR), which are involved in the release of the Ca2+ stored in sarcoplasmic reticulum has been clearly demonstrated. A biochemical test based on the analysis of the in vitro contracture response of muscular fibres to caffeine and halothane was developed to define the MHS status of patients. Although the genetic analysis of MHS has beneficiated from recent progresses, genetic testing is still far to answer to all testing situations. If in swine, hyperthermia syndrome was always associated with a unique mutation of the RyR1 gene, genetic analysis is far more complicated in human: i) more than 20 different MHS mutations in the RyR1 gene have been described; ii) a mutation of the gene encoding the dihydropyridine receptor has been identified; iii) 4 other potential MHS loci have been reported. 相似文献
5.
The RYR1 gene encodes the skeletal muscle isoform ryanodine receptor and is fundamental to the process of excitation-contraction coupling and skeletal muscle calcium homeostasis. Mapping to chromosome 19q13.2, the gene comprises 106 exons and encodes a protein of 5,038 amino acids. Mutations in the gene have been found in association with several diseases: the pharmacogenetic disorder, malignant hyperthermia (MH); and three congenital myopathies, including central core disease (CCD), multiminicore disease (MmD), and in an isolated case of a congenital myopathy characterized on histology by cores and rods. The majority of gene mutations reported are missense changes identified in cases of MH and CCD. In vitro analysis has confirmed that alteration of normal calcium homeostasis is a functional consequence of some of these changes. Genotype-phenotype correlation studies performed using data from MH and CCD patients have also suggested that mutations may be associated with a range of disease severity phenotypes. This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions. 相似文献
6.
Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families. 相似文献
7.
N Monnier N B Romero J Lerale P Landrieu Y Nivoche M Fardeau J Lunardi 《Human molecular genetics》2001,10(22):2581-2592
Central core disease (CCD) is an autosomal dominant congenital myopathy. Diagnosis is based on the presence of cores in skeletal muscles. CCD has been linked to the gene encoding the ryanodine receptor (RYR1) and is considered to be an allelic disease of malignant hyperthermia susceptibility. However, the report of a recessive form of transmission together with a variable clinical presentation has raised the question of the genetic heterogeneity of the disease. Analyzing a panel of 34 families exclusively recruited on the basis of both clinically and morphologically expressed CCD, 12 different mutations of the C-terminal domain of RYR1 have been identified in 16 unrelated families. Morphological analysis of the patients' muscles showed different aspects of cores, all of them associated with mutations in the C-terminal region of RYR1. Furthermore, we characterized the presence of neomutations in the RyR1 gene in four families. This indicates that neomutations into the RyR1 gene are not a rare event and must be taken into account for genetic studies of families that present with congenital myopathies type 'central core disease'. Three mutations led to the deletion in frame of amino acids. This is the first report of amino acid deletions in RYR1 associated with CCD. According to a four-transmembrane domain model, the mutations concentrated mostly in the myoplasmic and luminal loops linking, respectively, transmembrane domains T1 and T2 or T3 and T4 of RYR1. 相似文献
8.
Rueffert H Olthoff D Deutrich C Schober R Froster UG 《American journal of medical genetics. Part A》2004,(3):248-254
Malignant hyperthermia susceptibility (MHS) and central core disease (CCD) have been shown to result from missense mutations in the ryanodine receptor gene of the skeletal muscle (RYR1). A 15-year-old patient who had spondylocostal dysostosis (SCD) developed an MH crisis during general anesthesia. The patient was characterized phenotypically by block vertebrae, vertebral fusion, short neck and thorax, fused ribs, craniofacial abnormalities, spina bifida occulta, and a diaphragmatic defect closed surgically in early infancy. The diagnosis MH susceptible (MHS) was confirmed by the in vitro contracture test (IVCT) on a muscle biopsy. Surprisingly, the histopathological investigation revealed the presence of CCD too. Molecular genetic investigation of the RYR1 gene was performed to search for known MH-related mutations. Cluster regions of the RYR1 gene, in which mutations have already been found, were examined by direct automated sequencing. In addition to the diagnosis MHS and CCD we were able to identify a novel RYR1 mutation in exon 46: 7358ATC > ACC, resulting in an Ile2453Thr substitution. This mutation was also present in the mother, in whom MH disposition and CCD were determined by muscle investigations. We suggest that the newly identified RYR1 mutation is closely associated with MH and CCD. A probable causative role of the RYR1 gene in SCD patients should be assessed by further genetic investigations. 相似文献
9.
Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2) 总被引:26,自引:0,他引:26
Tiso N Stephan DA Nava A Bagattin A Devaney JM Stanchi F Larderet G Brahmbhatt B Brown K Bauce B Muriago M Basso C Thiene G Danieli GA Rampazzo A 《Human molecular genetics》2001,10(3):189-194
Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death. The disease locus was mapped to chromosome 1q42--q43. We report here on the physical mapping of the critical ARVD2 region, exclusion of two candidate genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families. In myocardial cells, the RyR2 protein, activated by Ca(2+), induces the release of calcium from the sarcoplasmic reticulum into the cytosol. RyR2 is the cardiac counterpart of RyR1, the skeletal muscle ryanodine receptor, involved in malignant hyperthermia (MH) susceptibility and in central core disease (CCD). The RyR2 mutations detected in the present study occurred in two highly conserved regions, strictly corresponding to those where mutations causing MH or CCD are clustered in the RYR1 gene. The detection of RyR2 mutations causing ARVD2, reported in this paper, opens the way to pre-symptomatic detection of carriers of the disease in childhood, thus enabling early monitoring and treatment. 相似文献
10.
Non-specific esterase, acid phosphotase, beta-glucoronidase, and N-acetyl-beta-glucosamindase were revealed using the histochemical method of asocombinations in biopsy specimens of the muscular tissue taken from 99 patients suffering from neurogenic and myogenic disorders. Biopsy specimens were taken also from 7 healthy persons. Concentrations of the granular product of the reaction correlated with autofluorescence in the same section. Some bioptic materials were investigated using electron-microscopy. It was established that activity of lysosomal hydrolases in the normal muscular tissue was low, being increased with age. Autofluorescence in the majority of cases was well noticible. In the groups of atrophic fibres in neurogenic atrophy there were observed focal elevation of the lysosomal enzymatic activity. Product of the reaction, which pointed to the activity of nonspecific esterase and acid phosphotase, was localized predominantly along the periphery of muscular fibres. Autofluorescence of the product of the reaction was considerable. On the other hand, there were extensive areas of muscular fibres in which the concentration of the reaction product did not exceed the normal level. Activity of hydrolases in cells of the mesenchyma was of a low degree. Ist type of the lysosomal activity was observed in myogenic dystrophy with an acute course of the disease; it was characterized by structural changes in the muscular tissue, activation of the all hydrolases under study, absence of autofluorescence on the areas of localization of the reaction product, participation of the mesenchyma cells in the lysosomal activation. IInd type of the lysosomal activity was noted in the muscular tissue in neurogenic atrophy. There was no difference in principle between neuro- and myogenic lesions as far as the type of lysosomal activity is concerned. Collation of the results obtained in the investigations with the data reported in available literature enabled the authors to put forward the concept of the two types of the lysosomal activity in muscular lesions: 1) diffuse elevation of the lysosome activity associated with structural changes in the muscular tissue; 2) focal elevation of the physiological activity due to formation of lipopigment. 相似文献
11.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that manifests in response to anesthetic triggering agents. Central core disease (CCD) is a myopathy closely associated with MH. Both MH and CCD are primarily disorders of calcium regulation in skeletal muscle. The ryanodine receptor (RYR1) gene encodes the key channel which mediates calcium release in skeletal muscle during excitation-contraction coupling, and mutations in this gene are considered to account for susceptibility to MH (MHS) in more than 50% of cases and in the majority of CCD cases. To date, 22 missense mutations in the 15,117 bp coding region of the RYR1 cDNA have been found to segregate with the MHS trait, while a much smaller number of these mutations is associated with CCD. The majority of RYR1 mutations appear to be clustered in the N-terminal amino acid residues 35-614 (MH/CCD region 1) and the centrally located residues 2163-2458 (MH/CCD region 2). The only mutation identified outside of these regions to date is a single mutation associated with a severe form of CCD in the highly conserved C-terminus of the gene. All of the RYR1 mutations result in amino acid substitutions in the myoplasmic portion of the protein, with the exception of the mutation in the C-terminus, which resides in the lumenal/transmembrane region. Functional analysis shows that MHS and CCD mutations produce RYR1 abnormalities that alter the channel kinetics for calcium inactivation and make the channel hyper- and hyposensitive to activating and inactivating ligands, respectively. The likely deciding factors in determining whether a particular RYR1 mutation results in MHS alone or MHS and CCD are: sensitivity of the RYR1 mutant proteins to agonists; the level of abnormal channel-gating caused by the mutation; the consequential decrease in the size of the releasable calcium store and increase in resting concentration of calcium; and the level of compensation achieved by the muscle with respect to maintaining calcium homeostasis. From a diagnostic point of view, the ultimate goal of development of a simple non-invasive test for routine diagnosis of MHS remains elusive. Attainment of this goal will require further detailed molecular genetic investigations aimed at solving heterogeneity and discordance issues in MHS; new initiatives aimed at identifying modulating factors that influence the penetrance of clinical MH in MHS individuals; and detailed studies aimed at describing the full epidemiological picture of in vitro responses of muscle to agents used in diagnosis of MH susceptibility. 相似文献
12.
Robinson RL Brooks C Brown SL Ellis FR Halsall PJ Quinnell RJ Shaw MA Hopkins PM 《Human mutation》2002,20(2):88-97
Malignant hyperthermia (MH) and central core disease (CCD) are autosomal dominant disorders of skeletal muscle. Susceptibility to MH is only apparent after exposure to volatile anesthetics and/or depolarizing muscle relaxants. CCD patients present with diffuse muscular weakness but are also at risk of MH. Mutations in RYR1 (19q13.1), encoding a skeletal muscle calcium release channel (ryanodine receptor), account for the majority of MH and CCD cases. Fifteen RYR1 N-terminal mutations are considered causative of MH susceptibility, five of which are also associated with CCD. In the first extensive UK population survey, eight of 15 mutations were detected in 85 out of 297 (29%) unrelated MH susceptible cases, with G2434R detected in 53 cases (18%). Mutation type was shown to affect significantly MH phenotypes (in vitro contracture test (IVCT) response to caffeine, halothane, and ryanodine). RYR1 mutations associated with both CCD and MH (R163C, R2163H, R2435H) had more severe caffeine and halothane response phenotypes than those associated with MH alone. Mutations near the amino terminal (R163C, G341R) had a relatively greater effect on responses to caffeine than halothane, with a significantly increased caffeine:halothane tension ratio compared to G2434R of the central domain. All phenotypes were more severe in males than females, and were also affected by muscle specimen size and viability. Discordance between RYR1 genotype and IVCT phenotype was observed in seven families (nine individuals), with five false-positives and four false-negatives. This represents the most extensive study of MH patient clinical and genetic data to date and demonstrates that RYR1 mutations involved in CCD are those associated with one end of the spectrum of MH IVCT phenotypes. 相似文献
13.
Rossi D De Smet P Lyfenko A Galli L Lorenzini S Franci D Petrioli F Orrico A Angelini C Tegazzin V Dirksen R Sorrentino V 《Journal of medical genetics》2007,44(2):e67
A novel single-nucleotide deletion in exon 100 of the RYR1 gene, corresponding to deletion of nucleotide 14,510 in the human RyR1 mRNA (c14510delA), was identified in a man with malignant hyperthermia and in his two daughters who were normal for malignant hyperthermia. This deletion results in a RyR1 protein lacking the last 202 amino acid residues. All three subjects heterozygotic for the mutated allele presented with a prevalence of type 1 fibres with central cores, although none experienced clinical signs of myopathy. Expression of the truncated protein resulted in non-functional RYR1 calcium release channels. Expression of wild-type and RyR1(R4836fsX4838) proteins resulted in heterozygotic release channels with overall functional properties similar to those of wild-type RyR1 channels. Nevertheless, small differences in sensitivity to calcium and caffeine were observed in heterotetrameric channels, which also presented an altered assembly/stability in sucrose-gradient centrifugation analysis. Altogether, these data suggest that altered RYR1 tetramer assembly/stability coupled with subtle chronic changes in Ca2+ homoeostasis over the long term may contribute to the development of core lesions and incomplete malignant hyperthermia susceptibility penetrance in individuals carrying this novel RYR1 mutation. 相似文献
14.
J A Snowden C A Angel D A Winfield J H Pringle K P West 《Journal of clinical pathology》1997,50(1):67-70
Angiotropic lymphoma, also known as intravascular lymphomatosis, is characterised by widespread intravascular proliferation of malignant lymphoid cells, usually without evidence of focal disease. A case of a 52 year old man referred for investigation of a two year history of pyrexia of unknown origin, skin rash and multiple organ failure is described. Angiotropic lymphoma was seen in gastric, colonic and skin biopsy specimens, and review of an earlier skin biopsy specimen showed similar morphological features. In contrast to previous cases which showed B or T cell differentiation, immunohistochemical examination was positive for histiocyte markers. Molecular studies showed no evidence of immunoglobulin heavy chain gene or T cell receptor gene rearrangement. The patient responded to combination chemotherapy, comprising cyclophosphamide, doxorubicin, etoposide, and prednisolone. This case highlights the fact that advanced lymphoma may be present without evidence of focal disease and that the diagnosis may be missed easily both clinically and histologically. 相似文献
15.
Collardeau-Frachon S Bouvier R Le Gall C Rivet C Cabet F Bellon G Lachaux A Scoazec JY 《Virchows Archiv : an international journal of pathology》2007,451(1):57-64
We report here four cases of pediatric patients in whom the diagnosis of cystic fibrosis was made only after the histological
examination of a liver specimen obtained by biopsy (three cases) or at autopsy (one case). There were two boys and two girls,
aged 13 months to 7.5 years. None had a personal or familial history suggestive of cystic fibrosis. One patient, presenting
with myocardial lesion and hepatomegaly, died of heart failure; at autopsy, the liver showed a typical aspect of focal biliary
cirrhosis. In the three other cases, liver disease was the only manifestation of cystic fibrosis at the time of diagnosis.
Liver biopsy examination showed focal biliary cirrhosis in one case and massive steatosis in two. In all four cases, the diagnosis
was confirmed by the existence of known pathogenic mutations in the CFTR gene. The evolution was variable; one patient had progressive liver disease with severe portal hypertension after 7 years;
another one had lung complications after 1 year. In conclusion, our experience recalls that the diagnosis of cystic fibrosis
must be considered in children presenting with unexplained liver disease; its confirmation by molecular techniques makes it
possible to set up an appropriate follow-up. 相似文献
16.
Keating Katherine E.; Quane Kathleen A.; Manning Bernadette M.; Lehane Mary; Hartung Edmund; Censier Kathrin; Urwyler Albert; Klausnitzer Monika; Muller Clemens R.; Heffron James J.A.; McCarthy Tommie V. 《Human molecular genetics》1994,3(10):1855-1858
Malignant hyperthermia (MH) is a potentially fatal autosomaldominant disorder of skeletal muscle and is triggered in susceptiblepeople by all commonly used inhalational anaesthetics and depolarizingmuscle relaxants. To date, six mutations in the skeletal muscleryanodine receptor gene (RYR1) have been identified in malignanthyperthermia susceptible (MHS) and central core disease (CCD)cases. Using SSCP analysis, we have screened the RYR1 gene inaffected individuals for novel MHS mutations and have identifieda G to A transition mutation which results in the replacementof a conserved Gly at position 2433 with an Arg. The Gly2433Argmutation was present in four of 104 unrelated MHS individualsinvestigated and was not detected in a normal population sample.This mutation is adjacent to the previously identified Arg2434Hismutation reported in a CCD/MH family and indicates that theremay be a second region in the RYR1 gene where MHS/CCD mutationscluster. 相似文献
17.
Treves S Vukcevic M Jeannet PY Levano S Girard T Urwyler A Fischer D Voit T Jungbluth H Lillis S Muntoni F Quinlivan R Sarkozy A Bushby K Zorzato F 《Human molecular genetics》2011,20(3):589-600
Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine receptor on the sarcoplasmic reticulum membrane. In this study, we directly measured excitation-coupled calcium entry by total internal reflection fluorescence microscopy in human skeletal muscle myotubes harbouring mutations in the RYR1 gene linked to malignant hyperthermia (MH) and central core disease (CCD). We found that excitation-coupled calcium entry is strongly enhanced in cells from patients with CCD compared with individuals with MH and controls. Furthermore, excitation-coupled calcium entry induces generation of reactive nitrogen species and enhances nuclear localization of NFATc1, which in turn may be responsible for the increased IL-6 released by myotubes from patients with CCD. 相似文献
18.
B. Bednář 《Virchows Archiv : an international journal of pathology》1979,382(3):313-322
Summary Typical epitheloid cell formations were found in 175 of 500 cases of various types of Hodgkin's disease. No distinctive behaviour was found in cases with epitheloid structures.Close attention has been devoted to a further series of 23 lymphoepitheloid cell malignant lymphomata marked by focal nuclear atypicality in their epitheloid cell granulomas, which destroyed the basic neoplastic structure of the lymph node in many cases, necessitating further biopsy. In this series not only Hodgkin's disease (7 cases) but also some malignant lymphomas of non Hodgkin's types (3 × immunoblastoma, 3 × immunocytoma and 2 × T-lymphoblastoma) were found. In 6 cases only a tentative diagnosis of lymphoepitheloid cell malignant lymphoma could be made.The epitheloid granulomatous reaction tended to disappear gradually in all cases by repeated check-ups, and was apparently a secondary phenomenon. The cause of the epitheloid cell atypia was not evident although it proved to be an important diagnostic feature identifying an independent form of lymphoepitheloid malignant lymphoma. The subsequent development of this lesion suggested a mildly pleiomorphic highly malignant lymphoma, which might be of B cell origin, but was sometimes demonstrably of the T cell series.List of Abbreviations Used HD
Hodgkin's disease
- ML
malignant lymphoma
- LML
lymphoepitheloid cell LM
- RS
Reed-Sternberg cells
- LH
lymphoid-histiocytic (polyploid variant of RS) cells
- HE
hematoxylin-eosin 相似文献
19.
Matti Haltia Anu Suomalainen Anna Majander Hannu Somer 《Brain pathology (Zurich, Switzerland)》1992,2(2):133-139
Multiple deletions of mitochondrial DNA (mtDNA) have recently been described in a number of patients with neurological disorders. Most cases have been clinically characterized by autosomal dominant inheritance, adult onset, and a slowly progressive course with external ophthalmoplegia and muscle weakness. Some patients have had evidence of central or peripheral nervous system involvement or episodes of myoglobinuria. Muscle biopsy findings include ragged-red fibres (RRF), muscle fibres with absent COX-activity and abundant abnormal mitochondria with paracrystalline inclusions. Biochemically, a generalized reduction in the activities of mtDNA-encoded enzymes is observed in skeletal muscle. Southern blotting or PCR analysis reveal multiple populations of deleted mtDNA. The deletions occur at multiple sites between the replication initiation sites, involving a large portion of mtDNA, and most deletions seem to be flanked by direct sequence repeats, shown to be "hot spots" in the case of single large deletions. Apparently, a defect in a nuclear gene results in multiple deletions of mtDNA. Both clinical, genetic and molecular genetic observations indicate heterogeneity of this new disease category, apparently based on a disturbance in the "cross-talk" between the nuclear and the mitochondrial genomes. 相似文献
20.
D Herlicoviez 《Pathologie-biologie》1975,23(2):107-117
Two cases, one being probably familial, of ocular myopathy are reported. In both the onset was in childhood by ptosis of the eyelids and the course lasted more than 20 years. The patients (32 and 49 years) presented involvement of the ocular muscles as well as of the facial, pharyngolaryngeal, neck and limb muscles. There was, in both cases, marked body weight loss which could not be explained by the muscular atrophy alone, and a thyroid nodule which was not accompanied by evident change in thyroid function. Muscle biopsy studies were carried out : electron microscopy showed in both cases aggregates of mitochondria exhibiting various changes ; in one case histochemistry demonstrated that these changes were confined to type 1 muscle fibres. These cases of descending ocular myopathy can be included therefore in the group of the smaller than myopathies with abnormal mitochondria greater than. 相似文献