A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially causative of malignant hyperthermia, central core disease, and severe skeletal malformation
| Autor: | Ralf Schober, Henrik Rueffert, C. Deutrich, Ursula G. Froster, Derk Olthoff |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Adolescent Genotype DNA Mutational Analysis Biology medicine.disease_cause Caffeine medicine Humans Point Mutation Missense mutation Myopathy Central Core Genetics (clinical) Family Health RYR1 Mutation Muscle biopsy Base Sequence medicine.diagnostic_test Point mutation Malignant hyperthermia Dysostoses Ryanodine Receptor Calcium Release Channel DNA Anatomy musculoskeletal system medicine.disease Spondylocostal dysostosis Musculoskeletal Abnormalities Pedigree Phenotype Female Halothane Malignant Hyperthermia Central core disease Muscle Contraction |
| Zdroj: | American Journal of Medical Genetics. :248-254 |
| ISSN: | 1096-8628 0148-7299 |
| DOI: | 10.1002/ajmg.a.20404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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