KCNJ2 Mutation Results in Andersen Syndrome with Sex-Specific Cardiac and Skeletal Muscle Phenotypes
AUTOR(ES)
Andelfinger, Gregor
FONTE
The American Society of Human Genetics
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=379203Documentos Relacionados
- Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)
- Sex-specific cognitive abnormalities in early-onset psychosis
- Maternal and Zygotic Sex-Specific Gene Interactions in DROSOPHILA MELANOGASTER
- SRY recognizes conserved DNA sites in sex-specific promoters.
- Sex-specific compensatory growth in food-deprived Nile tilapia