Background: Intellectual disability (ID) constitutes the most common group of neurodevelopmental disorders. Exome sequencing has enabled the discovery of genetic mutations responsible for a wide range of ID disorders.
Case presentation: In this study, we reported on two male siblings, aged 4 and 2 years, with motor and mental developmental delays and mild dysmorphic facial features. To identify the genetic causes of these symptoms, we employed trio-whole exome sequencing for the proband. We found a novel hemizygous missense variant in the PAK3 gene (c.1112G > A, p.Cys371Tyr), which encodes the p21-activated kinase 3, in the proband, which inherited from mother. The younger brother also has the hemizygous variant, which was confirmed by Sanger sequencing. The variant is located in the kinase domain and was regarded as a likely pathogenic variant in this family.
Conclusion: We diagnosed two male siblings with developmental delays as having a PAK3 likely pathogenic variant. This finding expands the list of PAK3 gene mutations associated with neurodevelopmental disorders and provides further details on its clinical features.
Keywords: Exome sequencing; Intellectual disability (ID); PAK3; Pathogenic variants.