Clinical, genetic, and histological features of centronuclear myopathy in the Netherlands

Autor: Anneke J. van der Kooi, Benno Küsters, Catharina G. Faber, Corien C. Verschuuren-Bemelmans, Corrie E. Erasmus, Nicol C. Voermans, Baziel G.M. van Engelen, Erik-Jan Kamsteeg, Heinz Jungbluth, Floor A. M. Duijkers, Bregje Jaeger, Meyke Schouten, Stacha F. I. Reumers, Karlijn Bouman, Maartje Pennings
Přispěvatelé: Pediatric surgery, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), Human Genetics, Neurology, ANS - Neuroinfection & -inflammation, Paediatric Neurology, EURO-NMD
Rok vydání: 2021
Předmět:
Male
Pathology
BIN1
Biopsy
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
centronuclear myopathy
Genes
X-Linked
RYR1
Medicine
Age of Onset
Child
Genetics (clinical)
Netherlands
Aged
80 and over
medicine.diagnostic_test
Histocytochemistry
CONGENITAL MYOPATHIES
Incidence
cohort
Middle Aged
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
Hypotonia
Phenotype
Child
Preschool
Female
medicine.symptom
Myopathies
Structural
Congenital
Adult
medicine.medical_specialty
MTM1
Adolescent
Genotype
MYOTONIC-DYSTROPHY
DISORDERS
MYOTUBULAR MYOPATHY
Other Research Donders Center for Medical Neuroscience [Radboudumc 0]
DYNAMIN 2
Exercise intolerance
FREQUENCY
Young Adult
Genetics
Humans
Genetic Predisposition to Disease
Centronuclear myopathy
Alleles
Genetic Association Studies
Aged
Muscle biopsy
business.industry
Genetic heterogeneity
MUTATIONS
Infant
Newborn
Infant
Muscle weakness
DNM2
medicine.disease
Congenital myopathy
Cross-Sectional Studies
Amino Acid Substitution
Mutation
business
Biomarkers
Zdroj: Clinical Genetics, 100(6), 692-702. Wiley
Clinical Genetics, 100, 6, pp. 692-702
Clinical Genetics, 100(6), 692-702. Wiley-Blackwell
Clinical genetics, 100(6), 692-702. Wiley-Blackwell
Clinical Genetics, 100, 692-702
Reumers, S F I, Erasmus, C E, Bouman, K, Pennings, M, Schouten, M, Kusters, B, Duijkers, F A M, van der Kooi, A, Jaeger, B, Verschuuren-Bemelmans, C C, Faber, C G, van Engelen, B G, Kamsteeg, E J, Jungbluth, H & Voermans, N C 2021, ' Clinical, genetic, and histological features of centronuclear myopathy in the Netherlands ', Clinical Genetics, vol. 100, no. 6, pp. 692-702 . https://doi.org/10.1111/cge.14054
ISSN: 0009-9163
DOI: 10.1111/cge.14054
Popis: Contains fulltext : 241356.pdf (Publisher’s version ) (Open Access) Centronuclear myopathy (CNM) is a genetically heterogeneous congenital myopathy characterized by muscle weakness, atrophy, and variable degrees of cardiorespiratory involvement. The clinical severity is largely explained by genotype (DNM2, MTM1, RYR1, BIN1, TTN, and other rarer genetic backgrounds), specific mutation(s), and age of the patient. The histopathological hallmark of CNM is the presence of internal centralized nuclei on muscle biopsy. Information on the phenotypical spectrum, subtype prevalence, and phenotype-genotype correlations is limited. To characterize CNM more comprehensively, we retrospectively assessed a national cohort of 48 CNM patients (mean age = 32 ± 24 years, range 0-80, 54% males) from the Netherlands clinically, histologically, and genetically. All information was extracted from entries in the patient's medical records, between 2000 and 2020. Frequent clinical features in addition to muscle weakness and hypotonia were fatigue and exercise intolerance in more mildly affected cases. Genetic analysis showed variants in four genes (18 DNM2, 14 MTM1, 9 RYR1, and 7 BIN1), including 16 novel variants. In addition to central nuclei, histologic examination revealed a large variability of myopathic features in the different genotypes. The identification and characterization of these patients contribute to trial readiness.
Databáze: OpenAIRE
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