title: Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.
abstract: The congenital myopathies are a group of disorders characterised by the predominance of specific histological features observed in biopsied muscle. Central core disease and nemaline myopathy are examples of congenital myopathies that have specific histological characteristics but significantly overlapping clinical pictures. Central core disease is an autosomal dominant disorder with variable penetrance which has been linked principally to the gene for the skeletal muscle calcium release channel (RYR1). Two recent reports have identified the 3' transmembrane domain of this gene as a common site for mutations. Two other studies have reported single families that have features of both central core disease and nemaline myopathy (core/rod disease) caused by mutations in RYR1. Screening of the 3' region (exons 93-105) of the RYR1 gene for mutations in 27 apparently unrelated patients with either central core disease or core/rod disease by single strand conformation polymorphism analysis and DNA sequencing identified three described and nine novel mutations in 15 patients.
authors.affiliation: Department of Anatomical Pathology, Royal Perth Hospital, Wellington Street,6000, Western Australia, Perth, Australia. mark.davis@health.wa.gov.au
authors.forename: M R
authors.initials: MR
authors.lastname: Davis
authors.forename: E
authors.initials: E
authors.lastname: Haan
authors.forename: H
authors.initials: H
authors.lastname: Jungbluth
authors.forename: C
authors.initials: C
authors.lastname: Sewry
authors.forename: K
authors.initials: K
authors.lastname: North
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: T
authors.initials: T
authors.lastname: Kuntzer
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authors.initials: P
authors.lastname: Lamont
authors.forename: A
authors.initials: A
authors.lastname: Bankier
authors.forename: P
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authors.lastname: Tomlinson
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
authors.forename: P
authors.initials: P
authors.lastname: Walsh
authors.forename: L
authors.initials: L
authors.lastname: Nagarajan
authors.forename: C
authors.initials: C
authors.lastname: Oley
authors.forename: A
authors.initials: A
authors.lastname: Colley
authors.forename: A
authors.initials: A
authors.lastname: Gedeon
authors.forename: R
authors.initials: R
authors.lastname: Quinlivan
authors.forename: J
authors.initials: J
authors.lastname: Dixon
authors.forename: D
authors.initials: D
authors.lastname: James
authors.forename: C R
authors.initials: CR
authors.lastname: Müller
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
mesh_terms: D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D020125:Mutation, Missense; D020512:Myopathy, Central Core / Q000235:genetics*; D010375:Pedigree; D010446:Peptide Fragments; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D010446:Peptide Fragments; D019837:Ryanodine Receptor Calcium Release Channel