IFT52 and Ciliopathy

This summary reviews the association between IFT52 (HGNC:15901) and ciliopathy (MONDO:0005308). Multiple independent studies provide convergent clinical and experimental evidence supporting an autosomal recessive pattern of inheritance, underscoring the relevance of IFT52 in ciliary function.

Affected individuals present with a constellation of features including pigmentary retinopathy (PMID:26880018), short stature (PMID:26880018), microdontia, skeletal dysplasia, narrow chest, and postaxial hand polydactyly. These clinical findings bolster the link between IFT52 dysfunction and ciliopathy phenotypes.

Genetic analyses across multiple reports have consistently identified biallelic mutations in IFT52. Notably, a recurrent nonsense variant, c.424C>T (p.Arg142Ter), has been documented in a consanguineous family as well as in additional unrelated probands (PMID:26880018; PMID:31042281). Additional variant types including missense changes further strengthen the genetic evidence for this association.

The autosomal recessive inheritance pattern is supported by segregation analyses within affected families, although detailed counts of additional affected relatives were not provided. Nonetheless, the consistency of biallelic alterations in IFT52 across independent cases enhances the confidence in its pathogenic role.

Functional experiments have demonstrated that IFT52 mutations lead to defective ciliary assembly and compromised protein stability. In vitro assays and zebrafish models, in particular, revealed impaired ciliogenesis that is concordant with clinical manifestations (PMID:30242358). This experimental evidence aligns with the genetic findings and provides mechanistic insight into the pathophysiology of ciliopathy.

Collectively, the convergence of segregation, genetic, and functional data categorizes the association between IFT52 and ciliopathy as Strong. This robust evidence not only supports accurate diagnostic decision‑making but also informs potential commercial applications and future research endeavors.

Key take‑home: IFT52 loss‑of‑function is a critical contributor to ciliopathy, affirming its importance in clinical assessment and targeted therapy development.

References

• Clinical Genetics • 2016 • A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy PMID:26880018
• Human Molecular Genetics • 2019 • Human IFT52 mutations uncover a novel role for the protein in microtubule dynamics and centrosome cohesion PMID:31042281
• Investigative Ophthalmology & Visual Science • 2018 • IFT52 as a Novel Candidate for Ciliopathies Involving Retinal Degeneration PMID:30242358

Evidence Based Scoring (AI generated)