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 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.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Plaster
authors.forename: R
authors.initials: R
authors.lastname: Tawil
authors.forename: M
authors.initials: M
authors.lastname: Tristani-Firouzi
authors.forename: S
authors.initials: S
authors.lastname: Canún
authors.forename: S
authors.initials: S
authors.lastname: Bendahhou
authors.forename: A
authors.initials: A
authors.lastname: Tsunoda
authors.forename: M R
authors.initials: MR
authors.lastname: Donaldson
authors.forename: S T
authors.initials: ST
authors.lastname: Iannaccone
authors.forename: E
authors.initials: E
authors.lastname: Brunt
authors.forename: R
authors.initials: R
authors.lastname: Barohn
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: F
authors.initials: F
authors.lastname: Deymeer
authors.forename: A L
authors.initials: AL
authors.lastname: George
authors.forename: F A
authors.initials: FA
authors.lastname: Fish
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.forename: A
authors.initials: A
authors.lastname: Nitu
authors.forename: C
authors.initials: C
authors.lastname: Ozdemir
authors.forename: P
authors.initials: P
authors.lastname: Serdaroglu
authors.forename: S H
authors.initials: SH
authors.lastname: Subramony
authors.forename: G
authors.initials: G
authors.lastname: Wolfe
authors.forename: Y H
authors.initials: YH
authors.lastname: Fu
authors.forename: L J
authors.initials: LJ
authors.lastname: Ptácek
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D017931:DNA Primers; D019066:Facies; D005192:Family Health; D005260:Female; D015870:Gene Expression; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009865:Oocytes / Q000502:physiology; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D018408:Patch-Clamp Techniques; D010375:Pedigree; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D015222:Sodium Channels / Q000235:genetics; D014981:Xenopus
chemical_list: D015220:Calcium Channels; D017931:DNA Primers; D062553:NAV1.4 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C106251:SCN4A protein, human; D015222:Sodium Channels