Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms

Vijeta Raghuram, Sydney Weber, Jacob Raber, Dong Hui Chen, Thomas D. Bird, James Maylie, John P. Adelman

Research output: Research - peer-reviewArticle

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 Ca2+-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.

LanguageEnglish (US)
Pages375-379
Number of pages5
JournalNeuroReport
Volume28
Issue number7
DOIs
StatePublished - 2017

Fingerprint

Mutation
Genes
Nonsense Codon
Brain
Exome
Transgenic Mice
Nucleotides
Phenotype

Keywords

  • apamin
  • ataxia
  • CRISPR-Cas system
  • human exome sequencing
  • neuroscience
  • SK potassium channel
  • transgenic mice
  • ZNF135

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms. / Raghuram, Vijeta; Weber, Sydney; Raber, Jacob; Chen, Dong Hui; Bird, Thomas D.; Maylie, James; Adelman, John P.

In: NeuroReport, Vol. 28, No. 7, 2017, p. 375-379.

Research output: Research - peer-reviewArticle

Raghuram V, Weber S, Raber J, Chen DH, Bird TD, Maylie J et al. Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms. NeuroReport. 2017;28(7):375-379. Available from, DOI: 10.1097/WNR.0000000000000754
Raghuram, Vijeta ; Weber, Sydney ; Raber, Jacob ; Chen, Dong Hui ; Bird, Thomas D. ; Maylie, James ; Adelman, John P./ Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms. In: NeuroReport. 2017 ; Vol. 28, No. 7. pp. 375-379
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