KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet 2002 Sep;71(3):663-8
Date
07/31/2002Pubmed ID
12148092Pubmed Central ID
PMC379203DOI
10.1086/342360Scopus ID
2-s2.0-0036724842 (requires institutional sign-in at Scopus site) 229 CitationsAbstract
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, clinodactyly, cleft palate, and scoliosis, which, together with cardiodysrhythmic periodic paralysis, have been termed "Andersen syndrome." However, no individual exhibited all manifestations of Andersen syndrome, and this diagnosis was not considered in the proband until other family members were examined. Other features seen in this kindred included unilateral dysplastic kidney and cardiovascular malformation (i.e., bicuspid aortic valve, bicuspid aortic valve with coarctation of the aorta, or valvular pulmonary stenosis), which have not been previously associated. Nonspecific electrocardiographic abnormalities were identified in some individuals, but none had a prolonged QT interval. Biophysical characterization of R67W demonstrated loss of function and a dominant-negative effect on Kir2.1 current. These findings support the suggestion that, in addition to its recognized role in function of cardiac and skeletal muscle, KCNJ2 plays an important role in developmental signaling.
Author List
Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL Jr, Benson DWMESH terms used to index this publication - Major topics in bold
Abnormalities, MultipleBase Sequence
Electric Conductivity
Electrocardiography
Female
Genotype
Heart Defects, Congenital
Humans
Male
Molecular Sequence Data
Muscle, Skeletal
Mutation, Missense
Pedigree
Phenotype
Potassium Channels, Inwardly Rectifying
Sex Characteristics
Syndrome
