title: [Molecular genetic analysis of the ryanodine receptor gene (RYR1) in Korean malignant hyperthermia families].
abstract: BACKGROUND
  Malignant hyperthermia (MH) is genetically heterogeneous, with mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) at 19q13.1 accounting for up to 80% of the cases. However, the search for known and novel mutations in the RYR1 gene is hampered by the fact that the gene contains 106 exons. We aimed to analyze mutations from the entire RYR1 coding region in Korean MH families.
  
  
  METHODS
  We investigated seven affected MH individuals and their family members. The entire RYR1 coding region from the genomic DNA was sequenced, and RYR1 haplotyping and mutational analysis were carried out.
  
  
  RESULTS
  We identified nine different RYR1 mutations or variations from seven Korean MH families. Among these, five previously reported mutations (p.Gly248Arg, p.Arg2435His, p.Arg2458His, p.Arg2676Trp, and p.Leu4838Val) and four novel variations of unknown significance (p.Arg2508Cys, p.Met4022Val, p.Glu2669Lys, and p.Ala4295Val) were identified. In two families, two variations (R2676W & M4022V, R2435H & A4295V, respectively) were identified simultaneously. Four of the observed nine mutations or variations were located outside the hotspot region of RYR1 mutations.
  
  
  CONCLUSIONS
  These data indicate that RYR1 is a main candidate gene in Korean MH families, and that comprehensive screening of the entire coding sequence of the RYR1 gene is necessary for molecular genetic investigations in MH-susceptible individuals, owing to the presence of RYR1 mutations or variations outside of the hotspot region.
authors.affiliation: Department of Forensic Medicine, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Dong Chan
authors.initials: DC
authors.lastname: Kim
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong Gon
authors.initials: YG
authors.lastname: Cho
authors.forename: Hye Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Sam Im
authors.initials: SI
authors.lastname: Choi
authors.forename: Dal Sik
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D056910:Republic of Korea; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel