Abstract OBJECTIVE: To identify the genetic defect causing a distal calf myopathy with cores. METHODS: Families with a genetically undetermined calf-predominant myopathy underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and muscle MRI. Next-generation sequencing and targeted Sanger sequencing were used to identify the causative genetic defect in each family. RESULTS: A novel deletion-insertion mutation in ryanodine receptor 1 (RYR1) was found in the proband of the index family and segregated with the disease in 6 affected relatives. Subsequently, we found 2 more families with a similar calf-predominant myopathy segregating with unique RYR1-mutated alleles. All patients showed a very slowly progressive myopathy without episodes of malignant hyperthermia or rhabdomyolysis. Muscle biopsy showed cores or core-like changes in all families. CONCLUSIONS: Our findings expand the spectrum of RYR1-related disorders to include a calf-predominant myopathy with core pathology and autosomal dominant inheritance. Two families had unique and previously unreported RYR1 mutations, while affected persons in the third family carried 2 previously known mutations in the same dominant allele. © 2019 American Academy of Neurology.

Jokela, M., Tasca, G., Vihola, A., Mercuri, E. M., Jonson, P., Lehtinen, S., Välipakka, S., Pane, M., Donati, M. B., Johari, M., Savarese, M., Huovinen, S., Isohanni, P., Palmio, J., Hartikainen, P., Udd, B., An unusual ryanodine receptor 1 (RYR1) phenotype: Mild, calf-predominant myopathy., <<NEUROLOGY. CLINICAL PRACTICE>>, 2019; (6): 7146-7249. [doi:10.1212/WNL.0000000000007246] [http://hdl.handle.net/10807/131793]

An unusual ryanodine receptor 1 (RYR1) phenotype: Mild, calf-predominant myopathy.

Tasca, Giorgio;Mercuri, Eugenio Maria;Pane, Marika;Donati, Maria Benedetta;
2019

Abstract

Abstract OBJECTIVE: To identify the genetic defect causing a distal calf myopathy with cores. METHODS: Families with a genetically undetermined calf-predominant myopathy underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and muscle MRI. Next-generation sequencing and targeted Sanger sequencing were used to identify the causative genetic defect in each family. RESULTS: A novel deletion-insertion mutation in ryanodine receptor 1 (RYR1) was found in the proband of the index family and segregated with the disease in 6 affected relatives. Subsequently, we found 2 more families with a similar calf-predominant myopathy segregating with unique RYR1-mutated alleles. All patients showed a very slowly progressive myopathy without episodes of malignant hyperthermia or rhabdomyolysis. Muscle biopsy showed cores or core-like changes in all families. CONCLUSIONS: Our findings expand the spectrum of RYR1-related disorders to include a calf-predominant myopathy with core pathology and autosomal dominant inheritance. Two families had unique and previously unreported RYR1 mutations, while affected persons in the third family carried 2 previously known mutations in the same dominant allele. © 2019 American Academy of Neurology.
2019
Inglese
Jokela, M., Tasca, G., Vihola, A., Mercuri, E. M., Jonson, P., Lehtinen, S., Välipakka, S., Pane, M., Donati, M. B., Johari, M., Savarese, M., Huovinen, S., Isohanni, P., Palmio, J., Hartikainen, P., Udd, B., An unusual ryanodine receptor 1 (RYR1) phenotype: Mild, calf-predominant myopathy., <<NEUROLOGY. CLINICAL PRACTICE>>, 2019; (6): 7146-7249. [doi:10.1212/WNL.0000000000007246] [http://hdl.handle.net/10807/131793]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/131793
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