Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9

  • Am J Hum Genet. 2008 Aug;83(2):193-9. doi: 10.1016/j.ajhg.2008.07.010.
Ortal Barel  1 ,  Stavit A Shalev ,  Rivka Ofir ,  Asi Cohen ,  Joel Zlotogora ,  Zamir Shorer ,  Galia Mazor ,  Gal Finer ,  Shareef Khateeb ,  Noam Zilberberg ,  Ohad S Birk
Affiliations
  • 1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva 84105, Israel.
PMID: 18678320 DOI: 10.1016/j.ajhg.2008.07.010
Abstract

We describe a maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KCNK9 within this locus. KCNK9 is maternally transmitted (imprinted with paternal silencing) and encodes K(2P)9.1, a member of the two pore-domain Potassium Channel (K(2P)) subfamily. The mutation fully abolishes the channel's currents--both when functioning as a homodimer or as a heterodimer with K(2P)3.1.