Assessment of mutations in KCNN2 and ZNF135 to patient neurological symptoms

作者：Raghuram Vijeta; Weber Sydney; Raber Jacob; Chen Dong Hui; Bird Thomas D; Maylie James; Adelman John P^*

来源：NeuroReport, 2017, 28(7): 375-379.

DOI：10.1097/WNR.0000000000000754

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

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.

• 出版日期2017-5-3