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Article: Mutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis

TitleMutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis
Authors
KeywordsHUMDISEASE
PROTEINS
SIGNALING
Issue Date2010
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2010, v. 140 n. 1, p. 88-98 How to Cite?
AbstractThyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis. © 2010 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/125053
ISSN
2023 Impact Factor: 45.5
2023 SCImago Journal Rankings: 24.342
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Muscular Dystrophy Association
National Institutes of HealthU54 RR19481
CAPES Foundation2284/01-4
FAPESP (Sao Paulo State Research Foundation)2000/03442-4
1999/03688-4
INSERM
AFM
C.B. Day Foundation
NINDS
Funding Information:

We thank Lily Jan, Friederike Haas, and Carol Vandenburg for helpful discussions and advice and all the patients for their participation. We also thank Kathleen Giacomini for additional DNA controls. This work was supported by the Muscular Dystrophy Association, National Institutes of Health grant U54 RR19481, CAPES Foundation grant 2284/01-4 (MRDS), and FAPESP (Sao Paulo State Research Foundation) grants 2000/03442-4 (MRDS) and 1999/03688-4 (RMBM). B. F. is supported by INSERM, AFM, and ANR Maladies Rares and acknowledges patient referral and fruitful discussions of members of the clinical and research French network Resocanaux. R. Brown received generous support from the C.B. Day Foundation and the NINDS L.J.P. is an Investigator of the Howard Hughes Medical Institute.

References

 

DC FieldValueLanguage
dc.contributor.authorRyan, DPen_HK
dc.contributor.authorDias da Silva, MRen_HK
dc.contributor.authorSoong, TWen_HK
dc.contributor.authorFontaine, Ben_HK
dc.contributor.authorDonaldson, MRen_HK
dc.contributor.authorKung, AWCen_HK
dc.contributor.authorJongjaroenprasert, Wen_HK
dc.contributor.authorLiang, MCen_HK
dc.contributor.authorKhoo, DHCen_HK
dc.contributor.authorCheah, JSen_HK
dc.contributor.authorHo, SCen_HK
dc.contributor.authorBernstein, HSen_HK
dc.contributor.authorMaciel, RMBen_HK
dc.contributor.authorBrown Jr, RHen_HK
dc.contributor.authorPtáček, LJen_HK
dc.date.accessioned2010-10-31T11:08:48Z-
dc.date.available2010-10-31T11:08:48Z-
dc.date.issued2010en_HK
dc.identifier.citationCell, 2010, v. 140 n. 1, p. 88-98en_HK
dc.identifier.issn0092-8674en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125053-
dc.description.abstractThyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis. © 2010 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellen_HK
dc.relation.ispartofCellen_HK
dc.subjectHUMDISEASEen_HK
dc.subjectPROTEINSen_HK
dc.subjectSIGNALINGen_HK
dc.subject.meshAmino Acid Sequence-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHypokalemic Periodic Paralysis - genetics - metabolism-
dc.subject.meshMutation-
dc.subject.meshPotassium Channels, Inwardly Rectifying - chemistry - genetics - metabolism-
dc.titleMutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysisen_HK
dc.typeArticleen_HK
dc.identifier.emailKung, AWC:awckung@hku.hken_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.cell.2009.12.024en_HK
dc.identifier.pmid20074522-
dc.identifier.pmcidPMC2885139-
dc.identifier.scopuseid_2-s2.0-73349132366en_HK
dc.identifier.hkuros174479en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73349132366&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume140en_HK
dc.identifier.issue1en_HK
dc.identifier.spage88en_HK
dc.identifier.epage98en_HK
dc.identifier.isiWOS:000273391900017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001454958-
dc.identifier.scopusauthoridRyan, DP=7402274953en_HK
dc.identifier.scopusauthoridDias da Silva, MR=6603057211en_HK
dc.identifier.scopusauthoridSoong, TW=7102415139en_HK
dc.identifier.scopusauthoridFontaine, B=7102625295en_HK
dc.identifier.scopusauthoridDonaldson, MR=7103330838en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK
dc.identifier.scopusauthoridJongjaroenprasert, W=6506678077en_HK
dc.identifier.scopusauthoridLiang, MC=36855099200en_HK
dc.identifier.scopusauthoridKhoo, DHC=7003466313en_HK
dc.identifier.scopusauthoridCheah, JS=55219860100en_HK
dc.identifier.scopusauthoridHo, SC=7403716889en_HK
dc.identifier.scopusauthoridBernstein, HS=7202733730en_HK
dc.identifier.scopusauthoridMaciel, RMB=8297878200en_HK
dc.identifier.scopusauthoridBrown Jr, RH=35359820600en_HK
dc.identifier.scopusauthoridPtáček, LJ=7007024949en_HK
dc.identifier.citeulike6516385-
dc.identifier.issnl0092-8674-

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