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Published on: August 20, 2019
Hemizygous splicing variant in CNKSR2 results in X-linked intellectual developmental disorder
Yuting Lou1, Xinglei Shi2, Guofa Su3
1Department of Pediatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Background:
Intellectual disability (ID) refers to a childhood-onset neurodevelopmental disorder with a prevalence of approximately 1%-3%.
Methods:
We performed whole exome sequencing for the patient with ID. And the splicing variant we found was validated by minigene assay.
Results:
Here, we report a boy with ID caused by a variant of CNKSR2. His neurological examination revealed hypsarrhythmia via electroencephalography and a right temporal polar arachnoid cyst via brain magnetic resonance imaging. A novel splicing variant in the CNKSR2 gene (NM_014927.5, c.1657+1G>A) was discovered by exome sequencing. The variant caused a 166 bp intron retention between exons 14 and 15, which was validated by a minigene assay. The variant was not reported in public databases such as gnomAD and the Exome Aggregation Consortium.
Conclusions:
The variant was predicted to be damaging to correct the translation of the CNKRS2 protein and was classified as likely pathogenic according to the ACMG guidelines.
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