PMID- 10599760
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 53
IP  - 9
DP  - 1999 Dec 10
TI  - A novel sodium channel mutation in a family with hypokalemic periodic paralysis.
PG  - 1932-6
AB  - OBJECTIVE: To identify the cause of hypokalemic periodic paralysis (HOKPP) in a 
      family whose disease is not caused by a mutation in the dihydropyridine-sensitive 
      (DHP) receptor alpha1-subunit gene (CACNA1S). BACKGROUND: Hypokalemic periodic 
      paralysis is primarily caused by mutations within CACNA1S. Genetic heterogeneity 
      for HOKPP has been reported, but no other locus has been identified. METHODS: 
      Single-stranded conformational polymorphism (SSCP) analysis and PCR direct 
      sequencing were used to screen the skeletal muscle alpha1-sodium channel gene 
      (SCN4A) for a mutation in our family. RESULTS: SSCP analysis showed an abnormally 
      migrating conformer in exon 12. Direct sequencing of the conformer showed a 
      guanine to adenine transition at position 2006 in the cDNA sequence; this results 
      in an amino acid substitution of a highly conserved arginine (Arg) to histidine 
      (His) at position 669. This sequence alteration segregated only with the affected 
      members of the kindred and was not found in a panel of 100 DNA samples from 
      healthy controls. The amino acid substitution alters the outermost positive 
      charge in the membrane spanning segment DII/S4, which is involved in voltage 
      sensing. CONCLUSIONS: The first arginine in DII/S4 and in DIV/S4 within the 
      skeletal muscle sodium channel and the L-type calcium channel genie CACNA1S 
      appear to be critical for normal function. In all four cases, Arg to His 
      mutations result in a disease phenotype. The identification of a mutation within 
      the skeletal muscle sodium channel resulting in hypokalemic periodic paralysis 
      represents a novel finding.
FAU - Bulman, D E
AU  - Bulman DE
AD  - Division of Neurology, Ottawa General Hospital, Ottawa Hospital Research 
      Institute, Ontario, Canada. dbulman@ogh.on.ca
FAU - Scoggan, K A
AU  - Scoggan KA
FAU - van Oene, M D
AU  - van Oene MD
FAU - Nicolle, M W
AU  - Nicolle MW
FAU - Hahn, A F
AU  - Hahn AF
FAU - Tollar, L L
AU  - Tollar LL
FAU - Ebers, G C
AU  - Ebers GC
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (NAV1.4 Voltage-Gated Sodium Channel)
RN  - 0 (SCN4A protein, human)
RN  - 0 (Sodium Channels)
RN  - 4QD397987E (Histidine)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence/genetics
MH  - Amino Acid Substitution/*genetics
MH  - Arginine/genetics
MH  - Electromyography
MH  - Histidine/genetics
MH  - Humans
MH  - Hypokalemic Periodic Paralysis/diagnosis/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - NAV1.4 Voltage-Gated Sodium Channel
MH  - Pedigree
MH  - Phenotype
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sodium Channels/*genetics
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1212/wnl.53.9.1932 [doi]
PST - ppublish
SO  - Neurology. 1999 Dec 10;53(9):1932-6. doi: 10.1212/wnl.53.9.1932.