IDENTIFICATION OF MUTATIONS IN THE CACNL1A3 GENE IN 13 FAMILIES OF SCANDINAVIAN ORIGIN HAVING HYPOKALEMIC PERIODIC PARALYSIS AND EVIDENCE OF A FOUNDER EFFECT IN DANISH FAMILIES

Familial hypokalemic periodic paralysis (hypoPP) is an autosomal domin ant disorder characterised by episodic attacks of paralysis of varying severity. Recently, linkage was found to markers in 1q31-32 and to th e gene encoding the muscle DHP-sensitive calcium channel alpha 1-subun it (CACNL1A3). Subsequently, three mutations in this gene were identif ied in patients with hypoPP: Arg528His, Arg1239His and Arg1239Gly. In this study, two different mutations were found in the CACNL1A3 gene in 13 Scandinavian families, 10 of whom have the Arg528His mutation whil e 3 families have the Arg1239His, Furthermore, there is evidence of a founder effect in 8 of the 9 Danish hypoPP families investigated, cons isting of haplotypes of microsatellite markers close to and within the CACNL1A3 gene and of the geographic origin of the families, For the f irst time, reduced penetrance in males with the Arg528His mutation was found in several cases. (C) 1997 Wiley-Liss, Inc.