title: Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms.
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-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.
authors.affiliation: aVollum Institute bDepartment of Behavioral Neuroscience cDepartment of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon dDepartment of Neurology, Geriatric Research (GRECC), VA Puget Sound Healthcare System, University of Washington, Seattle, Washington, USA.
authors.forename: Vijeta
authors.initials: V
authors.lastname: Raghuram
authors.forename: Sydney
authors.initials: S
authors.lastname: Weber
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Chen
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.forename: James
authors.initials: J
authors.lastname: Maylie
authors.forename: John P
authors.initials: JP
authors.lastname: Adelman
mesh_terms: D000328:Adult; D000818:Animals; D064113:CRISPR-Cas Systems; D015331:Cohort Studies; D005260:Female; D000072669:Gene Editing; D055879:Gene Knock-In Techniques; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C496897:KCNN2 protein, human; C496898:Kcnn2 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D051640:Small-Conductance Calcium-Activated Potassium Channels; C000625922:ZNF135 protein, human