scholarly journals Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark

2017 ◽  
Vol 3 (2) ◽  
pp. e140 ◽  
Author(s):  
Nanna Witting ◽  
Ulla Werlauff ◽  
Morten Duno ◽  
John Vissing
Keyword(s):  
Fiber Type ◽  
Adult Population ◽  
Congenital Myopathy ◽  
Compound Heterozygous ◽  
Walking Ability ◽  
Type I ◽  
Centronuclear Myopathy ◽  
Normal Limits ◽  
National Cohort ◽  
Nosologic Entity

Objective:Congenital myopathy as a nosologic entity has long been recognized, but knowledge of overall and subtype prevalence and phenotype-genotype relationship is scarce, especially in the adult population.Methods:A national cohort of 107 patients ≥5 years diagnosed with congenital myopathy were prospectively assessed clinically, histologically, and genetically.Results:Twenty-five patients were excluded because of atypical features or alternative etiologies. The remaining 82 were on average 28 years old. Histologic examination revealed 14 (17%) with core disease, 15 (18%) centronuclear myopathy, 12 (15%) nemaline rods, 27 (33%) congenital fiber-type disproportion or type I predominance, and 14 (17%) nonspecific myopathic changes. Genetic etiology was identified in 46 patients (56.1%); 22.0% were heterozygous or compound heterozygous for mutations in RYR1, 7.3% had DNM2 mutations, and 7.3% NEB mutations. Less than 5% had mutations in ACTA1, TPM2/3, MTM1, TTN, SEPN1, or SC4NA. A genetic cause was established in 83% with specific histology (cores/rods/centronuclear myopathy) vs 29% with unspecific histology. The detailed clinical examination found gene-dependent discrepancies in the pattern of muscle affection and walking ability. Although walking ability was delayed in patients with ACTA1, TPM2/3, and RYR1 mutations, it was within normal limits in patients with NEB and DNM2 mutations.Conclusions:We found that overall, genetic and histologic prevalence of congenital myopathy in Denmark differs from previous retrospective reports. Less RYR1 and more DNM2 and NEB mutations and less core histology were present in our cohort. These differences may be explained by our prospective design, the older cohort of patients, and by differences in genetic background.

scholarly journals Centronuclear myopathy: histopathological aspects in ten patients with chilfhood onset

1998 ◽  
Vol 56 (1) ◽  
pp. 01-08 ◽  
Author(s):  
EDMAR ZANOTELI ◽  
ACARY SOUZA BULLE OLIVEIRA ◽  
BEATRIZ HITOMI KIYOMOTO ◽  
BENY SCHMIDT ◽  
ALBERTO ALAIN GABBAI
Keyword(s):  
Ultrastructural Study ◽  
Fiber Type ◽  
Signs And Symptoms ◽  
Congenital Myopathy ◽  
Great Variability ◽  
Type I ◽  
Centronuclear Myopathy ◽  
Adult Onset ◽  
Childhood Onset

Centronuclear myopathy is a rare congenital myopathy. According to the period of onset of signs and symptoms and the degree of muscular involvement three clinical forms are distinguished: severe neonatal; childhood onset; and adult onset. We describe herein the muscle biopsy findings of ten patients with the childhood onset form of the disease including three cases with ultrastructural study. The biopsies disclosed increased nuclear centralization that varied from 25 to 90% of the fibers, type 1 predominance, great variability in fiber diameters, involvement in the internal fiber's architecture, and focal areas of myofilament disorganization. The main histopathologic differential diagnoses included type I fiber predominance, congenital fiber type disproportion, and myotonic dystrophy. The histologic abnormalities in centronuclear myopathy may be due to an arrest of maturation on the fetal myotubular stage. The cause of this arrest remains elusive.

scholarly journals Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gang Zhang ◽  
Min Xu ◽  
Tingting Huang ◽  
Wenxin Lin ◽  
Jinglin Chen ◽  
...  
Keyword(s):  
Motor Development ◽  
Lower Extremities ◽  
Average Diameter ◽  
Compound Heterozygous ◽  
Type I ◽  
Type Ii ◽  
Centronuclear Myopathy ◽  
Case Presentation ◽  
Muscle Disorders ◽  
Distal Muscle

Abstract Background Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported. Case presentation The child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy. Conclusions The clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.

Two Different UGT1A1 Mutations causing Crigler–Najjar Syndrome types I and II in an Iranian Family

2015 ◽  
Vol 24 (4) ◽  
pp. 523-526 ◽  
Author(s):  
Yoshihiro Maruo ◽  
Mahdiyeh Behnam ◽  
Shinichi Ikushiro ◽  
Sayuri Nakahara ◽  
Narges Nouri ◽  
...  
Keyword(s):  
Serum Bilirubin ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Compound Heterozygous ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Wild Type ◽  
Iranian Family ◽  
Udp Glucuronosyltransferase

Background: Crigler–Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.Case report: The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2. Results: The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%–36 % of the wild-type. Conclusion: Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2. Abbreviations: CN-1: Crigler–Najjar syndrome type I; CN-2: Crigler–Najjar syndrome type II; GS: Gilbert syndrome; UGT1A1: bilirubin UDP-glucuronosyltransferase; WT: Wild type; TB: total serum bilirubin.

scholarly journals Muscle Changes in Lambs with Surgically Created Scoliosis Produced in Utero

1978 ◽  
Vol 5 (3) ◽  
pp. 283-287 ◽  
Author(s):  
G.M. Kent ◽  
W. Zingg ◽  
D. Armstrong
Keyword(s):  
Musculoskeletal Diseases ◽  
Fiber Type ◽  
Surgical Techniques ◽  
Spinal Curvature ◽  
Surgical Trauma ◽  
Developmental Defect ◽  
Type I ◽  
Type Ii ◽  
Muscle Changes ◽  
Type Ii Fibers

SUMMARY:Spinal curves may be produced in fetal lambs with three surgical techniques. These procedures vary from mere exposure of the costo-vertebral junction of three ribs through a paravertebral incision, to resection of the head and part of the adjacent shaft of three ribs. The fetal age varies from forty-nine to seventy-three days. The degree of curvature present at birth seems to increase in severity with decreasing fetal age at the time of surgery, but the type of surgical procedure does not appear to influence the severity of the curve, suggesting that the mechanical presence of the ribs does not prevent the development of scoliosis in these animals.Histological studies of the m. longissimus dorsi at the apices of the curves reveal two main types of abnormality in the muscle fibers. Both Type I and Type II fibers were significantly reduced in size in the biopsies taken from the side on which the surgery was performed, and there was marked alteration in the proportion of one fiber type to the other in most biopsies taken from both operated sides when compared with biopsies from unoperated twin animals.The fetal age and amount of surgical trauma appeared to play no role in the degree of muscle alteration, suggesting that even minimal surgical trauma to the paraspinal region at any fetal age between 49–73 days is sufficient to produce significant muscle fiber abnormality and spinal curvature.A parallel is drawn between these muscle findings and those in a number of human musculoskeletal diseases, and suggests the possibility of a developmental defect in the pathogenesis of these diseases.

Myostatin regulates fiber-type composition of skeletal muscle by regulating MEF2 and MyoD gene expression

2009 ◽  
Vol 296 (3) ◽  
pp. C525-C534 ◽  
Author(s):  
Alex Hennebry ◽  
Carole Berry ◽  
Victoria Siriett ◽  
Paul O'Callaghan ◽  
Linda Chau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Target Genes ◽  
Fiber Type ◽  
Fiber Formation ◽  
Type I ◽  
Mobility Shift ◽  
Enhancer Activity ◽  
Fiber Type Composition ◽  
Nuclear Extracts ◽  
Type Composition

Myostatin (Mstn) is a secreted growth factor belonging to the tranforming growth factor (TGF)-β superfamily. Inactivation of murine Mstn by gene targeting, or natural mutation of bovine or human Mstn, induces the double muscling (DM) phenotype. In DM cattle, Mstn deficiency increases fast glycolytic (type IIB) fiber formation in the biceps femoris (BF) muscle. Using Mstn null (−/−) mice, we suggest a possible mechanism behind Mstn-mediated fiber-type diversity. Histological analysis revealed increased type IIB fibers with a concomitant decrease in type IIA and type I fibers in the Mstn−/−tibialis anterior and BF muscle. Functional electrical stimulation of Mstn−/−BF revealed increased fatigue susceptibility, supporting increased type IIB fiber content. Given the role of myocyte enhancer factor 2 (MEF2) in oxidative type I fiber formation, MEF2 levels in Mstn−/−tissue were quantified. Results revealed reduced MEF2C protein in Mstn−/−muscle and myoblast nuclear extracts. Reduced MEF2-DNA complex was also observed in electrophoretic mobility-shift assay using Mstn−/−nuclear extracts. Furthermore, reduced expression of MEF2 downstream target genes MLC1F and calcineurin were found in Mstn−/−muscle. Conversely, Mstn addition was sufficient to directly upregulate MLC promoter-enhancer activity in cultured myoblasts. Since high MyoD levels are seen in fast fibers, we analyzed MyoD levels in the muscle. In contrast to MEF2C, MyoD levels were increased in Mstn−/−muscle. Together, these results suggest that while Mstn positively regulates MEF2C levels, it negatively regulates MyoD expression in muscle. We propose that Mstn could regulate fiber-type composition by regulating the expression of MEF2C and MyoD during myogenesis.

Rostrocaudal pattern of fiber-type changes in an overloaded rat ankle extensor

1991 ◽  
Vol 71 (2) ◽  
pp. 558-564 ◽  
Author(s):  
P. F. Gardiner ◽  
B. J. Jasmin ◽  
P. Corriveau
Keyword(s):  
Fiber Type ◽  
Muscle Length ◽  
Similar Degree ◽  
Complex Nature ◽  
Type I ◽  
Fiber Types ◽  
Type Ii ◽  
Cross Sectional ◽  
Hypertrophic Response ◽  
Type I Fibers

Our aim was to quantify the overload-induced hypertrophy and conversion of fiber types (type II to I) occurring in the medial head of the gastrocnemius muscle (MG). Overload of MG was induced by a bilateral tenotomy/retraction of synergists, followed by 12–18 wk of regular treadmill locomotion (2 h of walking/running per day on 3 of 4 days). We counted all type I fibers and determined type I and II mean fiber areas in eight equidistant sections taken along the length of control and overloaded MG. Increase in muscle weights (31%), as well as in total muscle cross-sectional areas (37%) and fiber areas (type I, 57%; type II, 34%), attested to a significant hypertrophic response in overloaded MG. An increase in type I fiber composition of MG from 7.0 to 11.5% occurred as a result of overload, with the greatest and only statistically significant changes (approximately 70–100%) being found in sections taken from the most rostral 45% of the muscle length. Results of analysis of sections taken from the largest muscle girth showed that it significantly underestimated the extent of fiber conversion that occurred throughout the muscle as a whole. These data obtained on the MG, which possesses a compartmentalization of fiber types, support the notion that all fiber types respond to this model with a similar degree of hypertrophy. Also, they emphasize the complex nature of the adaptive changes that occur in these types of muscles as a result of overload.

Kinetics of muscle deoxygenation and microvascular Po2 during contractions in rat: comparison of optical spectroscopy and phosphorescence-quenching techniques

2012 ◽  
Vol 112 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Shunsaku Koga ◽  
Yutaka Kano ◽  
Thomas J. Barstow ◽  
Leonardo F. Ferreira ◽  
Etsuko Ohmae ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Visible Light ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Fiber Type ◽  
Type I ◽  
Phosphorescence Quenching ◽  
Mean Response Time ◽  
Muscle Deoxygenation ◽  
Visible Light Spectroscopy

The overarching presumption with near-infrared spectroscopy measurement of muscle deoxygenation is that the signal reflects predominantly the intramuscular microcirculatory compartment rather than intramyocyte myoglobin (Mb). To test this hypothesis, we compared the kinetics profile of muscle deoxygenation using visible light spectroscopy (suitable for the superficial fiber layers) with that for microvascular O2 partial pressure (i.e., PmvO2, phosphorescence quenching) within the same muscle region (0.5∼1 mm depth) during transitions from rest to electrically stimulated contractions in the gastrocnemius of male Wistar rats ( n = 14). Both responses could be modeled by a time delay (TD), followed by a close-to-exponential change to the new steady level. However, the TD for the muscle deoxygenation profile was significantly longer compared with that for the phosphorescence-quenching PmvO2 [8.6 ± 1.4 and 2.7 ± 0.6 s (means ± SE) for the deoxygenation and PmvO2, respectively; P < 0.05]. The time constants (τ) of the responses were not different (8.8 ± 4.7 and 11.2 ± 1.8 s for the deoxygenation and PmvO2, respectively). These disparate (TD) responses suggest that the deoxygenation characteristics of Mb extend the TD, thereby increasing the duration (number of contractions) before the onset of muscle deoxygenation. However, this effect was insufficient to increase the mean response time. Somewhat differently, the muscle deoxygenation response measured using near-infrared spectroscopy in the deeper regions (∼5 mm depth) (∼50% type I Mb-rich, highly oxidative fibers) was slower (τ = 42.3 ± 6.6 s; P < 0.05) than the corresponding value for superficial muscle measured using visible light spectroscopy or PmvO2 and can be explained on the basis of known fiber-type differences in PmvO2 kinetics. These data suggest that, within the superficial and also deeper muscle regions, the τ of the deoxygenation signal may represent a useful index of local O2 extraction kinetics during exercise transients.

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