Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a sporadic case of congenital muscular dystrophy (CMD) in a 13-year-old girl with early manifestation of muscle weakness and hypotonia, severe contractures, bulbar syndrome, progressive external ophtalmoplegia, and white matter changes on magnetic resonance imaging (MRI) of the brain, but no mental defect. Serum creatine kinase (CK) level was normal. Muscle biopsy revealed a dystrophic picture with a prominent inflammatory infiltrate mimicking inflammatory myopathy-typical histological findings in CMD. Immunostaining showed normal expression of merosin, alpha and beta-dystroglycans. Mutation analyses of calpain3, dysferlin, and SEPN1 genes were negative. An electron microscopy revealed the accumulation of abnormally enlarged mitochondria located under the sarcolemma. Measurement of respiratory chain enzyme activities did not reveal any biochemical defect and mitochondrial genetic studies, including sequencing of the entire mitochondrial genome, were unremarkable. Phenotypic presentation of our patient is very unusual and differs considerably from other CMD variants.
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PMID:An unusual case of congenital muscular dystrophy with normal serum CK level, external ophtalmoplegia, and white matter changes on brain MRI. 1739 6

Congenital myopathies describe a group of inherited muscle disorders with neonatal or infantile onset typically associated with muscle weakness, respiratory involvement and delayed motor milestones. We previously reported a novel congenital myopathy in an inbred Samaritan family. All patients displayed severe neonatal hypotonia and respiratory distress, and unlike other congenital myopathies, a constantly improving health status. As clinical and pathological data did not point to preferential candidate genes, we performed exome sequencing complemented by linkage analysis to identify the mutation causing the benign Samaritan congenital myopathy. We identified the homozygous p.Tyr1088Cys mutation in RYR1, encoding the skeletal muscle ryanodine receptor. This sarcoplasmic reticulum calcium channel is a key regulator of excitation-contraction coupling (ECC). Western blot and immunohistofluorescence revealed a significant decrease of the RYR1 protein level and an abnormal organization of skeletal muscle triad markers as caveolin-3, dysferlin and amphiphysin 2. RYR1 mutations are associated with different myopathies and malignant hyperthermia susceptibility. The index patient had mild hyperthermia following anesthesia, indicating that the inbred Samaritan population might be a risk group for this disorder. Our results suggest an aberrant ECC as the primary cause of this disease, and broaden the clinical consequences of RYR1 defects.
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PMID:Samaritan myopathy, an ultimately benign congenital myopathy, is caused by a RYR1 mutation. 2275 22