Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms. Issue 7 (3rd May 2017)

• Record Type: Journal Article
• Authors: Raghuram, Vijeta; Weber, Sydney; Raber, Jacob; Chen, Dong-Hui; Bird, Thomas D.; Maylie, James; Adelman, John P.
• Is Part Of: NeuroReport. Volume 28:Issue 7(2017)
• Publication Date: 2017-05-03
• Subjects: apamin -- ataxia -- CRISPR-Cas system -- human exome sequencing -- neuroscience -- SK potassium channel -- transgenic mice -- ZNF135; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000000754
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Exome sequencing from a patient with neurological and developmental symptoms revealed two mutations in separate genes. One was a homozygous transition mutation that results in an in-frame, premature translational stop codon in the ZNF135 gene predicted to encode a transcriptional repressor. Another mutation was heterozygous, a single nucleotide duplication in the KCNN2 gene that encodes a Ca 2+ -activated K + channel, SK2, and leads to a translational frame shift and a premature stop codon. Heterologous expression studies, brain slice recordings, and coordination tests from a transgenic mouse line carrying the SK2 mutation suggest that it does not contribute to the patient's symptoms. ZNF135 is expressed in human brain and it is likely that the homozygous mutation underlies the human phenotype.