TBL1Y: a new gene involved in syndromic hearing loss

  • Eur J Hum Genet. 2019 Mar;27(3):466-474. doi: 10.1038/s41431-018-0282-4.
Mariateresa Di Stazio  1 ,  Chiara Collesi  2  3 ,  Diego Vozzi  4  5 ,  Wei Liu  6 ,  Mike Myers  3 ,  Anna Morgan  2 ,  Pio Adamo D Adamo  2 ,  Giorgia Girotto  2 ,  Elisa Rubinato  2 ,  Mauro Giacca  2  3 ,  Paolo Gasparini  2
Affiliations
  • 1. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. [email protected].
  • 2. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
  • 3. Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149, Trieste, Italy.
  • 4. Medical Genetics, IRCCS Burlo Garofolo, Trieste, Italy.
  • 5. Division of Experimental Genetics, Sidra Medical & Research Center, Qatar Foundation, PO Box 26999, Doha, Qatar.
  • 6. Section of Otolaryngology, Department of Surgical Sciences, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
PMID: 30341416 DOI: 10.1038/s41431-018-0282-4
Abstract

Hereditary hearing loss (HHL) is an extremely heterogeneous disorder with autosomal dominant, recessive, and X-linked forms. Here, we described an Italian pedigree affected by HHL but also prostate hyperplasia and increased ratio of the free/total PSA levels, with the unusual and extremely rare Y-linked pattern of inheritance. Using exome Sequencing we found a missense variant (r.206A>T leading to p.Asp69Val) in the TBL1Y gene. TBL1Y is homologous of TBL1X, whose partial deletion has described to be involved in X-linked hearing loss. Here, we demonstrate that it has a restricted expression in adult human cochlea and prostate and the variant identified induces a lower protein stability caused by misfolded mutated protein that impairs its cellular function. These findings indicate that TBL1Y could be considered a novel candidate for HHL.