LINKAGE OF MALIGNANT HYPERTHERMIA AND HYPERKALEMIC PERIODIC PARALYSISTO THE ADULT SKELETAL-MUSCLE SODIUM-CHANNEL (SCN4A) GENE IN A LARGE PEDIGREE

Hyperkalemic periodic paralysis (HPP) is caused by mutations of the ad ult skeletal muscle sodium channel (SCN4A) gene on chromosome 17. Mali gnant hyperthermia (MH) is a genetically heterogeneous autosomal-domin ant disorder occurring in association with various neuromuscular disea ses or without other apparent abnormalities. In some families, MH is a ssociated with mutations of a calcium release channel (RYR1) gene on c hromosome 19. In other families, linkage of this disorder to the SCN4A gene on chromosome 17 has been suggested, We report on linkage analys is in a family in which both HPP and MH are inherited as autosomal-dom inant traits. Two polymorphisms within the SCN4A locus, an RFLP and a (C-A)(n) repeat, were typed on multiple family members. The findings w ere consistent with linkage of the polymorphic markers within the SCN4 A gene to both HPP (Z(max) = 6.79 at theta = 0.0) and MH (Z(max) = 1.7 6 at theta = 0) in this family. Our data provide further evidence that MH is linked to the SCN4A locus in some families. (C) 1998 Wiley-Liss , Inc.