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Novel skeletal muscle ryanodine receptor mutation in a large Brazilian family with malignant hyperthermia
Author(s) -
McWilliams S,
Nelson T,
Sudo RT,
ZapataSudo G,
Batti M,
Sambuughin N
Publication year - 2002
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2002.620111.x
Subject(s) - ryr1 , malignant hyperthermia , haplotype , ryanodine receptor , central core disease , genetics , biology , skeletal muscle , mutation , gene , endocrinology , medicine , receptor , genotype , pathology
Malignant hyperthermia (MH) is an autosomal dominant disorder that predisposes susceptible individuals to a potentially life‐threatening crisis when exposed to commonly used anesthetics. Mutations in the skeletal muscle calcium release channel, ryanodine receptor (RYR1) are associated with MH in over 50% of affected families. Linkage analysis of the RYR1 gene region at 19q13 was performed in a large Brazilian family and a distinct disease co‐segregating haplotype was revealed in the majority of members with diagnosis of MH. Subsequent sequencing of RYR1 mutational hot spots revealed a nucleotide substitution of C to T at position 7062, causing a novel amino acid change from Arg2355 to Cys associated with MH in the family. Haplotype analysis of the RYR1 gene area at 19q13 in the family with multiple MH members is an important tool in identification of genetic cause underlying this disease.