Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

Plaster N., Tawil R., Tristani-Firouzi M., Canun S., Bendahhou S., Tsunoda A., ...Daha Fazla

CELL, cilt.105, sa.4, ss.511-519, 2001 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 105 Sayı: 4
  • Basım Tarihi: 2001
  • Doi Numarası: 10.1016/s0092-8674(01)00342-7
  • Dergi Adı: CELL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.511-519
  • İstanbul Üniversitesi Adresli: Hayır

Özet

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 (maximum LOD = 3.23 at theta = 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 Andersen's 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.