1. TBL1Y: a new gene involved in syndromic hearing loss.
- Author
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Di Stazio M, Collesi C, Vozzi D, Liu W, Myers M, Morgan A, D Adamo PA, Girotto G, Rubinato E, Giacca M, and Gasparini P
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cochlea metabolism, Female, Genetic Diseases, Y-Linked pathology, Hearing Loss pathology, Humans, Male, Middle Aged, Mutation, Missense, Pedigree, Prostate metabolism, Prostatic Hyperplasia pathology, Protein Stability, Syndrome, Transducin metabolism, Genetic Diseases, Y-Linked genetics, Hearing Loss genetics, Prostatic Hyperplasia genetics, Transducin genetics
- 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.
- Published
- 2019
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