WDR13 – Intellectual Disability

The WDR13 gene, mapping to Xp11.23, encodes a six–WD–repeat nuclear protein broadly expressed across tissues, suggesting a regulatory role in cellular function (PMID:12659815). A hemizygous nonsense variant, c.757C>T (p.Arg253Ter), was identified by X‐chromosome exome sequencing in males from a single multiplex family with non-syndromic intellectual disability, consistent with X-linked recessive inheritance and segregation in the pedigree (PMID:34946860). Functional assays in patient fibroblasts revealed a >70% reduction in WDR13 transcript levels and dysregulation of established intellectual disability genes FMR1, SYN1, CAMK2A, and THOC2, supporting a loss‐of‐function mechanism (PMID:34946860).

Although evidence is currently limited to a single kindred, the truncating variant’s impact on transcript stability and downstream gene expression aligns with haploinsufficiency as a pathogenic mechanism. Additional unrelated cases and detailed phenotypic characterization are needed to refine the clinical spectrum. Nevertheless, WDR13 merits inclusion in diagnostic gene panels for X-linked intellectual disability, and functional assays should be considered for variant interpretation in clinical practice.

References

• Genomics • 2003 • A highly conserved human gene encoding a novel member of WD-repeat family of proteins (WDR13) PMID:12659815
• Genes • 2021 • WDR13: A Novel Gene Implicated in Non-Syndromic Intellectual Disability. PMID:34946860

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