A homozygous variant of WDR45B results in global developmental delay: Additional case and literature review

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.

Conclusion: We reported another case with a novel homozygous variant of WDR45B and showed the heterogeneity of clinical features.