CNKSR2 中的杂合剪接变异导致 X 连锁智力发育障碍。

Hemizygous splicing variant in CNKSR2 results in X-linked intellectual developmental disorder.

机构信息

Department of Pediatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Department of Pediatrics, Suichang Branch of the Second Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Mol Genet Genomic Med. 2024 Feb;12(2):e2389. doi: 10.1002/mgg3.2389.

DOI:10.1002/mgg3.2389

PMID:38337158

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10858311/

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.

摘要

背景

智力障碍（ID）是一种儿童期起病的神经发育障碍，患病率约为 1%-3%。

方法

我们对 ID 患者进行了全外显子组测序。我们发现的剪接变异通过微基因检测进行了验证。

结果

在此，我们报告了一名由 CNKSR2 变异引起的 ID 男孩。他的神经学检查显示脑电图存在高节律性，脑磁共振成像显示右侧颞极蛛网膜囊肿。通过外显子组测序发现 CNKSR2 基因（NM_014927.5，c.1657+1G>A）的一个新剪接变异。该变异导致第 14 号和第 15 号外显子之间 166bp 的内含子保留，微基因检测验证了这一结果。该变异未在 gnomAD 和外显子聚合联盟等公共数据库中报道。