Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: We reported another case with a novel homozygous variant of WDR45B and showed the heterogeneity of clinical features.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: We reported another case with a novel homozygous variant of WDR45B and showed the heterogeneity of clinical features.
摘要：
背景：全球发育迟缓（GDD）在患者中具有异质性的临床特征，约占儿童病例的1%-3%。越来越多的基因缺陷已被证明与GDD有关；到目前为止，只有有限的研究报告了由WDR45B引起的发育障碍。
方法：对患者及其家人进行三全外显子组测序（Trio-WES）。根据ACMG指南选择具有<0.01的次要等位基因频率的所有变体用于进一步解释。在她的家族中通过Sanger测序验证了候选致病变体。
结果：WDR45B中的纯合非同义变体[NM_019613.4：c.677G>C（p。Arg226Thr)]是从先证者中识别的。该变体在gnomAD和ExomeAggregationConsortium（ExAC）等已发布的数据库中不存在。根据ACMG指南,预测该变体对蛋白质具有损害性,并分类为VUS。我们回顾了文献，我们病例的发展延迟水平不如其他报告的病例严重。
结论：我们报告了另一例WDR45B的新型纯合变体，并显示了临床特征的异质性。
方法：对患者及其家人进行三全外显子组测序（Trio-WES）。根据ACMG指南选择具有<0.01的次要等位基因频率的所有变体用于进一步解释。在她的家族中通过Sanger测序验证了候选致病变体。
结果：WDR45B中的纯合非同义变体[NM_019613.4：c.677G>C（p。Arg226Thr)]是从先证者中识别的。该变体在gnomAD和ExomeAggregationConsortium（ExAC）等已发布的数据库中不存在。根据ACMG指南,预测该变体对蛋白质具有损害性,并分类为VUS。我们回顾了文献，我们病例的发展延迟水平不如其他报告的病例严重。
结论：我们报告了另一例WDR45B的新型纯合变体，并显示了临床特征的异质性。
