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Association of the causative malignant hyperthermia RyR1‐Thr2206Met‐mutation with discrete clinical and muscular biopsy changes
Author(s) -
Schober Ralf,
Ogunlade Vera,
Wehner Markus,
Rüffert Henrik
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.59.8
Subject(s) - ryr1 , malignant hyperthermia , central core disease , muscle biopsy , pathology , epigenetics , medicine , biopsy , genotype , biology , gene , genetics , receptor , ryanodine receptor
Malignant hyperthermia is a potentially fatal neuromuscular disease with hypersensitivity against anaesthetic agents, in the majority of cases based on mutations of the ryanodin receptor 1 gene (RyR1) in various loci. We have examined 17 out of 62 members of a family over 3 generations that had some accidents of narcosis and/or mild muscular symptoms in their anamnesis. In 8 of them there was a positive in‐vitro‐ contracture‐test, and direct sequencing of the RyR1‐gene revealed the c6617C>T (Thr2206Met) mutation exclusively in these patients. Histological, histochemical and immunohistological examination of the muscle biopsies revealed mild architectural changes and changes in the oxidative intermyofibrillar network of type 1 muscle fibers, being exclusively present in the malignant hyperthermia patients and most pronounced in the maternal grandfather. The changes were best visualized in NADH‐stains and did not correspond to classical central cores or multi‐minicores. Since a variety of genetic and epigenetic changes with clinical presentations different from the ones found by us have been described in these conditions, the report represents a novel aspect in the spectrum of malignant hyperthermia and will be helpful for the classification of RyR1 mutations and for genotype‐phenotype correlations.