Maternally Inherited Birk Barel Mental Retardation Dysmorphism Syndrome Caused by a Mutation in the Genomically Imprinted Potassium Channel KCNK9

Ortal Barel, Stavit A. Shalev, Rivka Ofir, Asi Cohen, Joel Zlotogora, Zamir Shorer, Galia Mazor, Gal Finer, Shareef Khateeb, Noam Zilberberg, Ohad S. Birk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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 ∼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 K2P9.1, a member of the two pore-domain potassium channel (K2P) subfamily. The mutation fully abolishes the channel's currents-both when functioning as a homodimer or as a heterodimer with K2P3.1.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalAmerican journal of human genetics
Volume83
Issue number2
DOIs
StatePublished - Aug 8 2008

Funding

We deeply thank the Morris Kahn Family Foundation for making this study possible. This work was also supported by grants from the Israel Science Foundation (431/03) and the Zlotowski Center for Neuroscience to N.Z. We thank Professor Hanna Mandel for the metabolic work-up; Professor Shapira for the analysis of muscle biopsies; Dr. Dan Reich and the team at the Department of Neonatology, Tal Shoshani, for technical assistance; Professor Juan (Moshe) Chemke, Professor Dvora Abeliovich, Dr. Morkos Siman, and Dr. Ahmed Haj-Daud for clinical insights; the families and patients; and the devoted family physicians and pediatricians responsible for the routine medical care of the family members in their communities.

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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