Hereditary isolated hearing loss is genetically highly heterogeneous. Over 100 genes are predicted to cause this disorder in humans. Sixty loci have been reported and 24 genes underlying 28 deafness forms have been identified. The present epistemic stage in the realm consists in a preliminary characterization of the encoded proteins and the associated defective biological processes. Since for several of the deafness forms we still only have fuzzy notions of their pathogenesis, we here adopt a presentation of the various deafness forms based on the site of the primary defect: hair cell defects, nonsensory cell defects, and tectorial membrane anomalies. The various deafness forms so far studied appear as monogenic disorders. They are all rare with the exception of one, caused by mutations in the gene encoding the gap junction protein connexin26, which accounts for between one third to one half of the cases of prelingual inherited deafness in Caucasian populations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1146/annurev.genet.35.102401.091224 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.
Elife
January 2025
Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, United States.
Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line.
View Article and Find Full Text PDFGenetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.
Hum Genet
January 2025
Division of Hearing and Balance Research, National Institute of Sensory Organs, NHO Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-Ku, Tokyo, 152-8902, Japan.
There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features.
View Article and Find Full Text PDFMYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea.
Proc Natl Acad Sci U S A
January 2025
School of Biosciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A is expressed in hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channels, thus setting their resting open probability (). However, direct evidence for this unique role for an unconventional myosin in mature hair cells is lacking.
View Article and Find Full Text PDFHuman TMC1 and TMC2 are mechanically gated ion channels.
Neuron
December 2024
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China; Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing, China; Institute for Medical Physiology, Chinese Institutes for Medical Research, Beijing, China. Electronic address:
Mammalian transmembrane channel-like proteins 1 and 2 (TMC1 and TMC2) have emerged as very promising candidate mechanotransduction channels in hair cells. However, controversy persists because the heterogeneously expressed TMC1/2 in cultured cells lack evidence of mechanical gating, primarily due to their absence from the plasma membrane. By employing domain swapping with OSCA1.
View Article and Find Full Text PDFVariants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.
Eur J Hum Genet
December 2024
Molecular, Cellular, and Genomic Biomedicine Group, IIS-La Fe, Valencia, Spain.
The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!