Hemizygous splicing variant in CNKSR2 results in X‐linked intellectual developmental disorder

Abstract

Abstract 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.

Keywords

• ACMG
• CNKSR2
• intellectual developmental
• variant
• X‐linked