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Dominant and recessive RYR1 mutations in adults with core lesions and mild muscle symptoms

Authors

  • Sofia T. Duarte MD,

    Corresponding author
    1. Neuropaediatrics Department, Hospital de D. Estefânia, Centro Hospitalar de Lisboa Central, E.P.E., Rua Jacinta Marto, 1169-045 Lisboa, Portugal
    2. CEDOC, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal
    • Neuropaediatrics Department, Hospital de D. Estefânia, Centro Hospitalar de Lisboa Central, E.P.E., Rua Jacinta Marto, 1169-045 Lisboa, Portugal
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  • Jorge Oliveira MSc,

    1. Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge I.P., Porto, Portugal
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  • Rośrio Santos MSc,

    1. Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge I.P., Porto, Portugal
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  • Pedro Pereira MSc,

    1. Neurology Department, Hospital Santa Maria, Lisboa, Portugal
    2. Neuromuscle Diseases Unit, Instituto de Medicina Molecular, Lisboa, Portugal
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  • Cândida Barroso MD,

    1. Neurology Department, Hospital Santa Maria, Lisboa, Portugal
    2. Neuromuscle Diseases Unit, Instituto de Medicina Molecular, Lisboa, Portugal
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  • Isabel Conceição MD,

    1. Neurology Department, Hospital Santa Maria, Lisboa, Portugal
    2. Neuromuscle Diseases Unit, Instituto de Medicina Molecular, Lisboa, Portugal
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  • Teresinha Evangelista MD

    1. Neurology Department, Hospital Santa Maria, Lisboa, Portugal
    2. Neuromuscle Diseases Unit, Instituto de Medicina Molecular, Lisboa, Portugal
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Abstract

Introduction:

Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH).

Methods:

Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed.

Results:

Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case.

Conclusions:

To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life-threatening reactions to general anesthesia. Muscle Nerve 44: 102–108, 2011

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