ZNF182 – Intellectual Disability

Two published case reports have implicated alterations encompassing ZNF182 (HGNC:13001) in individuals with intellectual disability (MONDO_0001071). In one study, a maternally inherited X‑linked deletion affecting the noncoding regulatory region between ZNF81 and ZNF182 was identified in twin boys with autism and intellectual disability (PMID:30559312). In a second report, a 335.4 kb microduplication at Xp11.2p11.3 spanning ZNF182 (among other genes) was detected in a 3‑year‑old boy presenting with developmental delay, autistic features, and growth retardation (PMID:22634100). Although these copy number variants provide preliminary genetic evidence, no isolated, canonical sequence variant (e.g. a coding change described in HGVS nomenclature) in ZNF182 has been reported to date.

The combined genetic findings yield a limited gene‑disease association, primarily based on CNV evidence that affects multiple genes. There are no functional studies or in vivo models directly demonstrating ZNF182’s role in the pathogenesis of intellectual disability. Additional, more definitive genetic and experimental studies are therefore needed to validate ZNF182 as a primary driver of the phenotype. Key take‑home: While current evidence suggests a potential contribution of ZNF182 disruptions to intellectual disability, its clinical utility remains preliminary and warrants further rigorous investigation.

References

• Cold Spring Harbor Molecular Case Studies • 2018 • Whole-genome sequencing in a family with twin boys with autism and intellectual disability suggests multimodal polygenic risk PMID:30559312
• Gene • 2012 • 335.4 kb microduplication in chromosome band Xp11.2p11.3 associated with developmental delay, growth retardation, autistic disorder and dysmorphic features PMID:22634100

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