Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP).
Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases known to involve an abnormal function of ion channels. The latter includes hypokalemic and hyperkalemic periodic paralyses, and non-dystrophic myotonias. We recently showed genetic linkage of hypoPP to loci on chromosome 1q31-32, co-localized with the DHP-sensitive calcium channel CACNL1A3. We propose to term this locus hypoPP-1. Using extended haplotypes with new markers located on chromosome 1q31-32, we now report the detailed mapping of hypoPP-1 within a 7 cM interval. Two recombinants between hypoPP-1 and the flanking markers D1S413 and D1S510 should help to reduce further the hypoPP-1 interval. We used this new information to demonstrate that a large family of French origin displaying hypoPP is not genetically linked to hypoPP-1. We excluded genetic linkage over the entire hypoPP-1 interval showing for the first time genetic heterogeneity in hypoPP.
Plassart
E
E
INSERM U134, Hôpital de la Salpêtrière, Paris, France.
Elbaz
A
A
Santos
J V
JV
Reboul
J
J
Lapie
P
P
Chauveau
D
D
Jurkat-Rott
K
K
Guimaraes
J
J
Saudubray
J M
JM
Weissenbach
J
J
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007008:Hypokalemia / Q000235:genetics; D008297:Male; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D010375:Pedigree; D011995:Recombination, Genetic