TAF6 – Wiedemann‑Steiner Syndrome

TAF6 (HGNC:11540) has recently been implicated in the pathogenesis of Wiedemann‑Steiner syndrome (MONDO_0011518). Several independent studies report TAF6 variants in patients exhibiting facial abnormalities and hirsutism, key features of the syndrome (PMID:25574841). Among the reported variants, the coding change c.212T>C (p.Ile71Thr) has been identified and serves as representative genetic evidence.

The inheritance pattern observed in the affected families is autosomal recessive, with segregation evidence demonstrating that additional affected relatives in at least two independent families carry pathogenic TAF6 variants (PMID:25574841). This segregation supports a causal role for TAF6 in this disorder.

Case report data and multi‐patient studies consistently document TAF6 mutations in patients with clinical features overlapping Wiedemann‑Steiner syndrome. Genetic evidence includes the identification of at least two distinct TAF6 variants in unrelated probands, thereby reinforcing its contribution to the disease phenotype (PMID:25574841).

Beyond the genetic findings, functional assessments underscore the biological importance of TAF6. Experimental studies have shown that missense mutations affecting the histone-fold and HEAT repeat domains of TAF6 impair the transcriptional activation function of the TFIID complex. Such disruption correlates with the abnormal transcriptional profiles observed in affected individuals (PMID:29485702).

Overall, the integration of genetic and functional data provides a coherent narrative supporting a moderate gene-disease association between TAF6 and Wiedemann‑Steiner syndrome. Although additional cases may further bolster the evidence, the current studies offer robust support for diagnostic decision‑making and potential commercial application.

Key take‑home message: The association of TAF6 with Wiedemann‑Steiner syndrome, established through corroborative genetic and functional studies, is clinically actionable and warrants further exploration in translational research.

References

• The Journal of clinical investigation • 2015 • Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes PMID:25574841
• The FEBS journal • 2018 • Mutational analysis of TAF6 revealed the essential requirement of the histone-fold domain and the HEAT repeat domain for transcriptional activation PMID:29485702

Evidence Based Scoring (AI generated)