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Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion
Author(s) -
Clarke Nigel F.,
Waddell Leigh B.,
Cooper Sandra T.,
Perry Margaret,
Smith Robert L.L.,
Kornberg Andrew J.,
Muntoni Francesco,
Lillis Suzanne,
Straub Volker,
Bushby Kate,
Guglieri Michela,
King Mary D.,
Farrell Michael A.,
Marty Isabelle,
Lunardi Joel,
Monnier Nicole,
North Kathryn N.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21278
Subject(s) - ryr1 , biology , genetics , mutation , autosomal recessive inheritance , gene , ryanodine receptor , intracellular
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 causeof CFTD and can be associated with extreme fiber size disproportion. © 2010 Wiley‐Liss, Inc.