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 similar 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 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.