Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.
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.
Barel
Ortal
O
The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva 84105, Israel.
Shalev
Stavit A
SA
Ofir
Rivka
R
Cohen
Asi
A
Zlotogora
Joel
J
Shorer
Zamir
Z
Mazor
Galia
G
Finer
Gal
G
Khateeb
Shareef
S
Zilberberg
Noam
N
Birk
Ohad S
OS
D000818:Animals; D002898:Chromosomes, Human, Pair 8; D005260:Female; D008040:Genetic Linkage; D018392:Genomic Imprinting; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009035:Mothers; D009154:Mutation; D011110:Polymorphism, Genetic; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics*; D013577:Syndrome; D014982:Xenopus laevis
C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain