2. Academic Validation
  3. TBL1Y: a new gene involved in syndromic hearing loss

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

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.

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