Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores.
Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores.
复制标题
恶性高热中 RYR1 基因的突变筛查：在具有相关中央核心的家系中检测新的 Tyr 至 Ser 突变。
作者：
K. Quane;Katherine E. Keating;J. Healy;Bernadette M. Manning;Renee Krivosic;I. Krivosic;Nicole Monnier;Joël Lunardi;Tommie V. McCarthy
兰尼碱受体基因（Ryanodine receptor gene，RYR 1）在少数恶性高热（malignant hyperthermia，MH）家系中发生突变。该基因的错义突变也在两个患有中央核心病（CCD）的家族中被发现，CCD是一种与MH密切相关的罕见肌病。在努力确定其他RYR 1突变负责MH和CCD，我们使用了SSCP的方法来筛选RYR 1基因的突变在一个家庭表现出易感性MH（MHS），其中一些MHS个人显示核心区域在他们的肌肉。一个独特的异常SSCP的序列分析，使我们能够确定一个点突变共分离与MHS在所描述的家庭。该突变将位置522处的保守酪氨酸残基改变为丝氨酸残基。该突变位于迄今已知的六种MHS/CCD突变中的五种附近，并提供了MHS/CCD突变可能聚集在RYR 1蛋白的氨基末端区域的进一步证据。
The ryanodine receptor gene (RYR1) has been shown to be mutated in a small number of malignant hyperthermia (MH) pedigrees. Missense mutations in this gene have also been identified in two families with central core disease (CCD), a rare myopathy closely associated with MH. In an effort to identify other RYR1 mutations responsible for MH and CCD, we used a SSCP approach to screen the RYR1 gene for mutations in a family exhibiting susceptibility to MH (MHS) where some of the MHS individuals display core regions in their muscle. Sequence analysis of a unique aberrant SSCP has allowed us to identify a point mutation cosegregating with MHS in the described family. The mutation changes a conserved tyrosine residue at position 522 to a serine residue. This mutation is positioned relatively close to five of the six MHS/CCD mutations known to date and provides further evidence that MHS/CCD mutations may cluster in the amino terminal region of the RYR1 protein.