Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

Nikki M. Plaster; Rabi Tawil; Martin Tristani-Firouzi; Sonia Canún; Sad Bendahhou; Akiko Tsunoda; Matthew R. Donaldson; Susan T. Iannaccone; Ewout Brunt; Richard Barohn; John Clark; Feza Deymeer; Alfred L. George; Frank A. Fish; Angelika Hahn; Alexandru Nitu; Coskun Ozdemir; Piraye Serdaroglu; S. H. Subramony; Gil Wolfe; Ying Hui Fu; Louis J. Ptáček

doi:10.1016/S0092-8674(01)00342-7

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

Nikki M. Plaster, Rabi Tawil, Martin Tristani-Firouzi, Sonia Canún, Sad Bendahhou, Akiko Tsunoda, Matthew R. Donaldson, Susan T. Iannaccone, Ewout Brunt, Richard Barohn, John Clark, Feza Deymeer, Alfred L. George, Frank A. Fish, Angelika Hahn, Alexandru Nitu, Coskun Ozdemir, Piraye Serdaroglu, S. H. Subramony, Gil WolfeYing Hui Fu, Louis J. Ptáček^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

866 Scopus citations

Abstract

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 (maximum LOD = 3.23 at θ = 0 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.

Original language	English (US)
Pages (from-to)	511-519
Number of pages	9
Journal	Cell
Volume	105
Issue number	4
DOIs	https://doi.org/10.1016/S0092-8674(01)00342-7
State	Published - May 18 2001

Funding

The authors are grateful to the families who participated in this work and to Anthea Letsou, Robert Ruff, and Mike Sanguinetti for helpful discussions and critical review of this manuscript. We thank Carol Vandenberg for the Kir 2.1 cDNA clone, Monica Lin, Catherine McKenna, Judy Jensen, Linda Ballard, and the Genomics Core Facility of the Huntsman Cancer Institute for technical assistance. This investigation was supported by the Muscular Dystrophy Association (L.J.P. and R.T.), NIH grant NS38616 (Y-H.F. and L.J.P.), and Public Health Service research grant M01-RR00064 from the National Center for Research Resources. L.J.P. is an Investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(01)00342-7

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Plaster, N. M., Tawil, R., Tristani-Firouzi, M., Canún, S., Bendahhou, S., Tsunoda, A., Donaldson, M. R., Iannaccone, S. T., Brunt, E., Barohn, R., Clark, J., Deymeer, F., George, A. L., Fish, F. A., Hahn, A., Nitu, A., Ozdemir, C., Serdaroglu, P., Subramony, S. H., ... Ptáček, L. J. (2001). Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell, 105(4), 511-519. https://doi.org/10.1016/S0092-8674(01)00342-7

@article{c231a7cf237c43a486fbb3e14bc62bf1,

title = "Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome",

abstract = "Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 (maximum LOD = 3.23 at θ = 0 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.",

author = "Plaster, {Nikki M.} and Rabi Tawil and Martin Tristani-Firouzi and Sonia Can{\'u}n and Sad Bendahhou and Akiko Tsunoda and Donaldson, {Matthew R.} and Iannaccone, {Susan T.} and Ewout Brunt and Richard Barohn and John Clark and Feza Deymeer and George, {Alfred L.} and Fish, {Frank A.} and Angelika Hahn and Alexandru Nitu and Coskun Ozdemir and Piraye Serdaroglu and Subramony, {S. H.} and Gil Wolfe and Fu, {Ying Hui} and Pt{\'a}{\v c}ek, {Louis J.}",

note = "Funding Information: The authors are grateful to the families who participated in this work and to Anthea Letsou, Robert Ruff, and Mike Sanguinetti for helpful discussions and critical review of this manuscript. We thank Carol Vandenberg for the Kir 2.1 cDNA clone, Monica Lin, Catherine McKenna, Judy Jensen, Linda Ballard, and the Genomics Core Facility of the Huntsman Cancer Institute for technical assistance. This investigation was supported by the Muscular Dystrophy Association (L.J.P. and R.T.), NIH grant NS38616 (Y-H.F. and L.J.P.), and Public Health Service research grant M01-RR00064 from the National Center for Research Resources. L.J.P. is an Investigator of the Howard Hughes Medical Institute.",

year = "2001",

month = may,

day = "18",

doi = "10.1016/S0092-8674(01)00342-7",

language = "English (US)",

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pages = "511--519",

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Plaster, NM, Tawil, R, Tristani-Firouzi, M, Canún, S, Bendahhou, S, Tsunoda, A, Donaldson, MR, Iannaccone, ST, Brunt, E, Barohn, R, Clark, J, Deymeer, F, George, AL, Fish, FA, Hahn, A, Nitu, A, Ozdemir, C, Serdaroglu, P, Subramony, SH, Wolfe, G, Fu, YH & Ptáček, LJ 2001, 'Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome', Cell, vol. 105, no. 4, pp. 511-519. https://doi.org/10.1016/S0092-8674(01)00342-7

TY - JOUR

T1 - Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

AU - Plaster, Nikki M.

AU - Tawil, Rabi

AU - Tristani-Firouzi, Martin

AU - Canún, Sonia

AU - Bendahhou, Sad

AU - Tsunoda, Akiko

AU - Donaldson, Matthew R.

AU - Iannaccone, Susan T.

AU - Brunt, Ewout

AU - Barohn, Richard

AU - Clark, John

AU - Deymeer, Feza

AU - George, Alfred L.

AU - Fish, Frank A.

AU - Hahn, Angelika

AU - Nitu, Alexandru

AU - Ozdemir, Coskun

AU - Serdaroglu, Piraye

AU - Subramony, S. H.

AU - Wolfe, Gil

AU - Fu, Ying Hui

AU - Ptáček, Louis J.

N1 - Funding Information: The authors are grateful to the families who participated in this work and to Anthea Letsou, Robert Ruff, and Mike Sanguinetti for helpful discussions and critical review of this manuscript. We thank Carol Vandenberg for the Kir 2.1 cDNA clone, Monica Lin, Catherine McKenna, Judy Jensen, Linda Ballard, and the Genomics Core Facility of the Huntsman Cancer Institute for technical assistance. This investigation was supported by the Muscular Dystrophy Association (L.J.P. and R.T.), NIH grant NS38616 (Y-H.F. and L.J.P.), and Public Health Service research grant M01-RR00064 from the National Center for Research Resources. L.J.P. is an Investigator of the Howard Hughes Medical Institute.

PY - 2001/5/18

Y1 - 2001/5/18

N2 - Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 (maximum LOD = 3.23 at θ = 0 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.

AB - Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 (maximum LOD = 3.23 at θ = 0 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.

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DO - 10.1016/S0092-8674(01)00342-7

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SN - 0092-8674

VL - 105

SP - 511

EP - 519

JO - Cell

JF - Cell

IS - 4

ER -

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

Abstract

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