50例恶性高热患者中RYR1基因106个外显子的突变频率及定位

Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.

作者信息

Galli Lucia, Orrico Alfredo, Lorenzini Stefania, Censini Stefano, Falciani Michela, Covacci Antonello, Tegazzin Vincenzo, Sorrentino Vincenzo

机构信息

Molecular Medicine Section, Department of Neuroscience, University of Siena and Azienda Ospedaliera Universitaria Senese, Siena, Italy.

出版信息

Hum Mutat. 2006 Aug;27(8):830. doi: 10.1002/humu.9442.

DOI:10.1002/humu.9442

PMID:16835904

Abstract

Malignant hyperthermia (MH) is a dominantly inherited pharmacogenetic condition that manifests as a life-threatening hypermetabolic reaction when a susceptible individual is exposed to common volatile anesthetics and depolarizing muscle relaxants. Although MH appears to be genetically heterogeneous, RYR1 is the main candidate for MH susceptibility. However, since molecular analysis is generally limited to exons where mutations are more frequently detected, these are routinely found only in 30-50% of susceptible subjects. In this study the entire RYR1 coding region was analyzed in a cohort of 50 Italian MH susceptible (MHS) subjects. Thirty-one mutations, 16 of which were novel, were found in 43 individuals with a mutation detection rate of 86%, the highest reported for RYR1 in MH so far. These data provide clear evidence that mutations in the RYR1 gene are the predominant cause of MH.

摘要

恶性高热（MH）是一种常染色体显性遗传的药物遗传学疾病，当易感个体接触常见挥发性麻醉剂和去极化肌肉松弛剂时，会表现为危及生命的高代谢反应。尽管MH在遗传上似乎具有异质性，但RYR1是MH易感性的主要候选基因。然而，由于分子分析通常仅限于更频繁检测到突变的外显子，因此这些突变通常仅在30%至50%的易感个体中被常规发现。在本研究中，对50名意大利MH易感（MHS）个体组成的队列进行了RYR1编码区全序列分析。在43名个体中发现了31个突变，其中16个是新突变，突变检出率为86%，是迄今为止报道的RYR1在MH中的最高检出率。这些数据提供了明确的证据，表明RYR1基因突变是MH的主要病因。