Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Pediatrics, Hengshui people's Hospital, Hengshui, Hebei, China.
Mol Genet Genomic Med. 2022 Oct;10(10):e2036. doi: 10.1002/mgg3.2036. Epub 2022 Aug 13.
Global developmental delay (GDD) has a heterogeneous clinical profile among patients, accounting for approximately 1%-3% of cases in children. An increasing number of gene defects have been demonstrated to be associated with GDD; up to now, only limited studies have reported developmental disorders driven by WDR45B.
Trio-whole exome sequencing (Trio-WES) was performed for the patient and her family. All variants with a minor allele frequency <0.01 were selected for further interpretation according to the ACMG guidelines. Candidate pathogenic variants were validated by Sanger sequencing in her family.
A homozygous nonsynonymous variant in WDR45B [NM_019613.4: c.677G>C (p. Arg226Thr)] was identified from the proband. The variant was absent in published databases such as gnomAD and Exome Aggregation Consortium (ExAC). The variant was predicted to be damaging for proteins and classified as VUS according to the ACMG guidelines. We reviewed the literature, and the development delay level in our case was less severe than the other reported cases.
We reported another case with a novel homozygous variant of WDR45B and showed the heterogeneity of clinical features.
全球发育迟缓（GDD）在患者中有不同的临床表现，约占儿童病例的 1%-3%。越来越多的基因缺陷已被证明与 GDD 相关；迄今为止，仅有有限的研究报告了由 WDR45B 驱动的发育障碍。
对患者及其家系进行了三人全外显子组测序（Trio-WES）。根据 ACMG 指南，选择次要等位基因频率<0.01 的所有变体进行进一步解释。在家系中通过 Sanger 测序验证候选致病性变体。
从先证者中鉴定出 WDR45B 中的纯合错义变异 [NM_019613.4: c.677G>C (p. Arg226Thr)]。该变体在 gnomAD 和 Exome Aggregation Consortium (ExAC) 等已发表数据库中不存在。该变体预测对蛋白质具有破坏性，并根据 ACMG 指南分类为 VUS。我们回顾了文献，我们的病例中的发育迟缓程度不如其他报道的病例严重。
我们报告了另一个携带 WDR45B 新型纯合变异的病例，并显示了临床特征的异质性。
Zotero 插件