Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome

Leomar Y Ballester; D Woodrow Benson; Brenda Wong; Ian H Law; Katherine D Mathews; Carlos G Vanoye; Alfred L George Jr

doi:10.1002/humu.9418

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Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome

Journal article

Open access

Peer reviewed

Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome

Leomar Y Ballester, D Woodrow Benson, Brenda Wong, Ian H Law, Katherine D Mathews, Carlos G Vanoye and Alfred L George Jr

Human mutation, Vol.27(4), pp.388-388

04/2006

DOI: 10.1002/humu.9418

PMID: 16541386

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Abstract

Mutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, have been identified in Andersen syndrome (or Andersen-Tawil syndrome), an inherited disorder characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We identified and characterized two novel KCNJ2 mutations (c.220A>G/p.T74A and c.443G>C/p.G144A) associated with Andersen syndrome. Heterologous expression of a recombinant wild type human KCNJ2 cDNA (WT-KCNJ2) in HEK-293 cells results in robust inward rectifying currents, but we did not observe measurable currents from cells expressing either mutant. Cells co-transfected with WT-KCNJ2 and either mutant exhibited substantially lower whole-cell current amplitude consistent with a dominant-negative suppression of WT-KCNJ2 by the mutant channels. Both p.T74A and p.G144A exhibit robust plasma membrane expression, but a third previously reported allele (p.C101R) exhibited impaired trafficking. Our results demonstrate functional consequences of two novel trafficking-competent KCNJ2 mutations associated with Andersen syndrome and expand our knowledge of allelic diversity in this disease.

Gene Expression

Amino Acid Sequence

Humans

Models, Molecular

Molecular Sequence Data

Male

Potassium Channels, Inwardly Rectifying - genetics

Mutation - genetics

Potassium Channels, Inwardly Rectifying - chemistry

Protein Transport

DNA Mutational Analysis

Pedigree

Electrocardiography

Female

Child

Andersen Syndrome - genetics

Details

Title: Subtitle: Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome
Creators: Leomar Y Ballester - Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37027-0275, USA
D Woodrow Benson
Brenda Wong
Ian H Law
Katherine D Mathews
Carlos G Vanoye
Alfred L George Jr
Resource Type: Journal article
Publication Details: Human mutation, Vol.27(4), pp.388-388
DOI: 10.1002/humu.9418
PMID: 16541386
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: HL69712 / NHLBI NIH HHS HL68880 / NHLBI NIH HHS NS07491 / NINDS NIH HHS
Language: English
Date published: 04/2006
Academic Unit: Neurology; Cardiology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020605802771

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