Author/Authors :
Nikki M. Plaster، نويسنده , , Rabi Tawil، نويسنده , , Martin Tristani-Firouzi، نويسنده , , Sonia Can?n، نويسنده , , Saïd Bendahhou، نويسنده , , Akiko Tsunoda، نويسنده , , Matthew R. Donaldson، نويسنده , , Susan T. Iannaccone، نويسنده , , Ewout Brunt، نويسنده , , Richard Barohn، نويسنده , , John Clark، نويسنده , , Feza Deymeer، نويسنده , , Alfred L. George Jr، نويسنده , , Frank A. Fish، نويسنده , , Angelika Hahn، نويسنده , , Alexandru Nitu، نويسنده , , Coskun Ozdemir، نويسنده , , Piraye Serdaroglu، نويسنده , , S.H. Subramony، نويسنده , , Gil Wolfe، نويسنده , , et al.، نويسنده ,
Abstract :
Andersenʹs syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersenʹs locus to chromosome 17q23 maximum LOD = 3.23 at θ = 0 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 Andersenʹs 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.
