title: Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.
abstract: The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of type 1 (slow twitch) fibers compared to type 2 (fast twitch) fibers. To investigate whether mutations in RYR1 are a cause of CFTD we sequenced RYR1 in seven CFTD families in whom the other known causes of CFTD had been excluded. We identified compound heterozygous changes in the RYR1 gene in four families (five patients), consistent with autosomal recessive inheritance. Three out of five patients had ophthalmoplegia, which may be the most specific clinical indication of mutations in RYR1. Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1 are a relatively common cause of CFTD and can be associated with extreme fiber size disproportion.
authors.affiliation: Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, Australia. NigelC@chw.edu.au
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Clarke
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Waddell
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Cooper
authors.forename: Margaret
authors.initials: M
authors.lastname: Perry
authors.forename: Robert L L
authors.initials: RL
authors.lastname: Smith
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kornberg
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lillis
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Michela
authors.initials: M
authors.lastname: Guglieri
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
authors.forename: Michael A
authors.initials: MA
authors.lastname: Farrell
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marty
authors.forename: Joel
authors.initials: J
authors.lastname: Lunardi
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel