EVIDENCE FOR THE LOCALIZATION OF A MALIGNANT HYPERTHERMIA SUSCEPTIBILITY LOCUS (MHS2) TO HUMAN CHROMOSOME-17Q

被引:109
作者
LEVITT, RC
OLCKERS, A
MEYERS, S
FLETCHER, JE
ROSENBERG, H
ISAACS, H
MEYERS, DA
机构
[1] JOHNS HOPKINS MED INST,DEPT MED,BALTIMORE,MD 21205
[2] UNIV WITWATERSRAND,DEPT PHYSIOL,JOHANNESBURG 2001,SOUTH AFRICA
[3] HAHNEMANN UNIV,DEPT ANESTHESIOL,PHILADELPHIA,PA 19102
[4] UNIV PRETORIA,DEPT HUMAN GENET & DEV BIOL,PRETORIA,SOUTH AFRICA
关键词
D O I
10.1016/S0888-7543(05)80152-1
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Malignant hyperthermia susceptibility is a lethal autosomal dominant disorder of skeletal muscle metabolism that is triggered by all potent inhalation anesthetic gases. Recent linkage studies suggest a genetic locus for this disorder on 19q13.1. We have previously reported three unrelated families diagnosed with MHS that are unlinked to markers surrounding this locus on 19q13.1. In this report we extend these observations and present linkage studies on 16 MHS families. Four families (25%) were found linked to the region 19q12-q13.2 (Zmax = 2.96 with the ryanodine receptor at θ = 0.0). Five families (31%) were found closely linked to the anonymous marker NME1 (previously designated NM23) on chromosome 17q11.2-q24 (Zmax = 3.26 at θ = 0.0). Two families (13%) were clearly unlinked to either of these chromosomal regions. In five additional families, data were insufficient to determine their linkage status (they were potentially linked to two or more sites). The results of our heterogeneity analyses are consistent with the hypothesis that MHS can be caused in humans by any one of at least three distinct genetic loci. Furthermore, we provide preliminary linkage data suggesting the localization of a gene in human MHS to 17q11.2-q24 (MHS2), with a gene frequency of this putative locus approximately equal to that of the MHS1 locus on 19q. © 1992 Academic Press, Inc. All rights reserved.
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页码:562 / 566
页数:5
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