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.
Original language | English |
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Pages (from-to) | 466-474 |
Number of pages | 9 |
Journal | European Journal of Human Genetics |
Volume | 27 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2019 |
Keywords
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Cochlea/metabolism
- Female
- Genetic Diseases, Y-Linked/*genetics/pathology
- Hearing Loss/*genetics/pathology
- Humans
- Male
- Middle Aged
- Mutation, Missense
- Pedigree
- Prostate/metabolism
- Prostatic Hyperplasia/*genetics/pathology
- Protein Stability
- Syndrome
- Transducin/*genetics/metabolism