Analysis of genetic linkage in malignant hyperthermia susceptible families in Japan

日本恶性高热易感家族遗传连锁分析

基本信息

批准号：
06671527
负责人：
KAWAMOTO Masashi
金额：
$ 1.09万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671527/
关键词：
Malignant hyperthermia Gene Genetic linkage analysis Skeletal muscle Skinned fiber PCR リアノジン受容体 Ca-induced Ca release

项目摘要

By using linkage-analysis of RYR1 gene polymorphism, we investigated the relation between genetic evidence of RYR1 abnormalities and accelerated rate of Ca-induced Ca release (CICR) mechanism of sarcoplasmic reticulum in skeletal muscle from malignant hyperthermia susceptible (MHS) subjects and families in Japan. Of 72 subjects referred to our institute for further investigation of MHS,26 subjects received skeletal muscle biopsy for the measurement of CICR rate by the skinned fiber method. By sampling venous blood, DNA samples were also obtained from the subjects in these 26 unrelated families. Analyzes of restriction fragment length polymorphism (RFLP) on RYR1 locus and hypervariable microsatellite were performed to investigate the relation between RYR1 abnormalities and acceleration of CICR rate.Accelerated CICR rate was observed in 4 subjects who presented clinically fulminant malignant hyperthemia (MH) and in their 3 relatives. Analysis for substitution of C1840T was performed in 72 subjects, while no alteration was demonstrated. However, we could determine one family as MHS because informative polymorphism suggested the linkage between the acceleration of CICR rate and RYR1 gene. In this family, the linkage study of RYR1 gene would be useful for further investigation of MHS.If the relation is determined between heterogeneity of MH and acceleration of CICR rate, we believe that the genetic test could replace the CICR test as a diagnostic tool for MH.Because occurrence of MH is rare (1 of 74,000 general anesthesias) and a few of MHS subjects may receive the invasive muscle biopsy, we conclude that it is necessary to improve the genetic test and to determine the relation for the investigation of MH in Japan.

通过使用RYR1基因多态性的链接分析，我们研究了RyR1异常的遗传证据与CA诱导的CA释放的加速速率（CICR）的加速速率（CICR）机制在骨骼肌中，骨骼肌肉中骨骼肌肉中骨骼肌肉中骨骼肌的骨骼肌肉中的骨骼肌肉中的骨骼肌肉中的骨骼肌肉和骨骼肌肉骨骼疾病（MHS）易于（MHS）受试者（MHS）受试者（MHS（MHS）为MHS）。在我们研究所的72名受试者中，有26名受试者接受了通过皮肤纤维方法测量CICR率的骨骼肌活检。通过取样静脉血，还从这26个无关家族中的受试者中获得了DNA样品。对RYR1基因座和高变量的微卫星进行限制片段长度多态性（RFLP）的分析进行了研究，以研究RYR1异常和CICR速率加速之间的关系。在4个受试者中观察到CICR速率的加速性CICR速率，这些受试者在临床上表现出了4个受试者，这些受试者均表现为临床上临床上的恶性超霉素（MMH）和他们的3个受试者。在72名受试者中进行了C1840T替代的分析，但未证明任何改变。但是，我们可以确定一个家庭为MHS，因为信息性多态性表明CICR速率的加速度与RYR1基因之间的联系。 In this family, the linkage study of RYR1 gene would be useful for further investigation of MHS.If the relation is determined between heterogeneity of MH and acceleration of CICR rate, we believe that the genetic test could replace the CICR test as a diagnostic tool for MH.Because occurrence of MH is rare (1 of 74,000 general anesthesias) and a few of MHS subjects may receive the invasive muscle biopsy,我们得出的结论是，有必要改善基因检测并确定日本研究MH的关系。