TAF6 – Alazami-Yuan syndrome

TAF6 encodes a core subunit of the TFIID transcription factor complex and has been implicated in Alazami-Yuan syndrome, a rare autosomal recessive disorder characterized by rapid pubertal development, Cornelia de Lange–like facial features, and normal intelligence (PMID:35317131). To date, only a single 11-year-old boy meeting diagnostic criteria has been described.

Genetic analysis revealed a compound heterozygous TAF6 genotype consisting of c.76A>T (p.Met26Leu) and c.1052delT (p.Ile351ThrfsTer?), inherited from clinically unaffected parents, supporting segregation under an autosomal recessive model (PMID:35317131). No additional probands or unrelated families have been reported, limiting the genetic evidence. Functional assays in yeast further demonstrate that mutations in the histone-fold domain and HEAT repeat domain abrogate transcriptional activation, consistent with a loss-of-function mechanism, but human cell or animal models are lacking (PMID:29485702). Overall, the association currently meets a Limited clinical validity rating. Further case reports, segregation analyses, and in vivo functional studies are required. Key take-home: biallelic TAF6 variants should be considered in diagnostic testing for Alazami-Yuan syndrome.

References

• World journal of clinical cases • 2022 • Novel compound heterozygous variants in the TAF6 gene in a patient with Alazami-Yuan syndrome: A case report. PMID:35317131
• 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

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