2002
DOI: 10.1086/342360
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KCNJ2 Mutation Results in Andersen Syndrome with Sex-Specific Cardiac and Skeletal Muscle Phenotypes

Abstract: Evaluation of candidate loci culminated in the identification of a heterozygous missense mutation (R67W) in KCNJ2, the gene encoding the inward-rectifying potassium current, Kir2.1, in 41 members of a kindred in which ventricular arrhythmias (13 of 16 female members [81%]) and periodic paralysis (10 of 25 male members [40%]) segregated as autosomal dominant traits with sex-specific variable expressivity. Some mutation carriers exhibited dysmorphic features, including hypertelorism, small mandible, syndactyly, … Show more

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Cited by 229 publications
(172 citation statements)
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“…Patients with Andersen-Tawil syndrome having the heterozygous mis-sense mutation R67W in KCNJ2 have been found to display nonspecific ECG abnormalities but no QT prolongation, despite a history of syncope and frequent ventricular premature beats. 6 Biophysical characterization of R67W demonstrated loss of function and a dominant-negative effect on Kir2.1 current. In contrast to the clinical experience, our results demonstrate that I K1 block consistently prolongs APD and QT interval.…”
Section: Discussion Cellular and Ionic Basis For Andersen-tawil Syndromementioning
confidence: 99%
See 1 more Smart Citation
“…Patients with Andersen-Tawil syndrome having the heterozygous mis-sense mutation R67W in KCNJ2 have been found to display nonspecific ECG abnormalities but no QT prolongation, despite a history of syncope and frequent ventricular premature beats. 6 Biophysical characterization of R67W demonstrated loss of function and a dominant-negative effect on Kir2.1 current. In contrast to the clinical experience, our results demonstrate that I K1 block consistently prolongs APD and QT interval.…”
Section: Discussion Cellular and Ionic Basis For Andersen-tawil Syndromementioning
confidence: 99%
“…[1][2][3][4][5][6] This skeletal muscle syndrome is associated with periodic paralysis often linked to fluctuations in plasma potassium levels. 2,7,8 Clinical studies indicate that Andersen-Tawil syndrome may be associated with arrhythmias, particularly when aggravated by other health problems such as infection.…”
Section: Introductionmentioning
confidence: 99%
“…There is still no consensus as to the possible sex-dependent effect of the KCNJ2 mutation and the likelihood of expressing BVT. Andelfinger et al 8 described a 71-member family with clinical and genetically defined ATS1 in which 13 (81%) of 16 mutation-positive females expressed BVT compared with none present in the 25 mutation-positive males. Other studies exploring phenotypic variability concluded that no sex-dependent phenotypic differences were present in ATS1.…”
Section: Cardiac Manifestationsmentioning
confidence: 99%
“…tissues (7, 16, 22, 40 -49). However, experiments in heterologous expression systems have shown them to act as specific dominant-negative suppressors of their functional counterparts (7,16,22,42,(45)(46)(47)(48). Since SK3-1C did not produce functional channels when expressed heterologously in mammalian cells (data not shown), we used the approach described for other non-functional K ϩ channel isoforms to ascertain whether SK3-1C exhibits dominantinhibitory activity.…”
Section: Sk3-1c Transcripts Are Present In Human Hematopoietic and Mumentioning
confidence: 99%
“…Similar truncation mutants of Kv1.1 underlie episodic ataxia type-1 (49,64), and truncation mutants of KCNQ2 and KCNQ3 are responsible for benign familial neonatal convulsion. Dominant-inhibitory nonfunctional mutants of K ir 2.1/KCNJ2 contribute to Andersen's syndrome, a developmental disorder with an accompanying ventricular tachycardia (48). Thus, dominant-negative suppression may be a widespread phenomenon through which the functional expression of multimeric proteins such as K ϩ channels is regulated, leading to gradations in the levels of membrane excitability.…”
Section: Dominant-negative Suppression By Sk3-1c Is Associated With Imentioning
confidence: 99%