title: 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.
abstract: Familial hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder characterised by episodic attacks of paralysis of varying severity. Recently, linkage was found to markers in 1q31-32 and to the gene encoding the muscle DHP-sensitive calcium channel alpha 1-subunit (CACNL1A3). Subsequently, three mutations in this gene were identified 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 while 3 families have the Arg1239His. Furthermore, there is evidence of a founder effect in 8 of the 9 Danish hypoPP families investigated, consisting of haplotypes of microsatellite markers close to and within the CACNL1A3 gene and of the geographic origin of the families. For the first time, reduced penetrance in males with the Arg528His mutation was found in several cases.
authors.affiliation: Department of Clinical Genetics, University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Sillén
authors.forename: T
authors.initials: T
authors.lastname: Sørensen
authors.forename: I
authors.initials: I
authors.lastname: Kantola
authors.forename: M L
authors.initials: ML
authors.lastname: Friis
authors.forename: K H
authors.initials: KH
authors.lastname: Gustavson
authors.forename: C
authors.initials: C
authors.lastname: Wadelius
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004276:DNA, Satellite; D003718:Denmark; D005190:Family; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D010375:Pedigree; D012537:Scandinavian and Nordic Countries
chemical_list: D015220:Calcium Channels; D004276:DNA, Satellite