TABLE 1.
Cloned nonsyndromic deafness genes and their phenotypes
| Phenotype |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Disease (OMIM) |
Locus | Gene (OMIM) |
Chromosome location |
Gene | Protein | Predicted function |
Age of onset | Affected frequency |
Vestibular involvement |
| #124900 | DFNA1 | 602121 | 5q31 | DIAPH1 | Hu homolog of D.
melanogaster Diaphanous gene |
Cytokinesis and cell polarity; regulation of actin polymerization in hair cells of the inner ear |
0–20 | Low to all | |
| #600101 | DFNA2 | 603324 | 1p35.1 | GJB3 | Connexin 31 | Gap junction protein | 20–40 | High | |
| #600101 | DFNA2 | 603537 | 1p34 | KCNQ4 | KCNQ4 | Voltage-gated potassium channel |
10–30 | High | |
| #601544 | DFNA3 | 121011 | 13q11-12 | GJB2 | Connexin 26 | Gap junction protein | 0–20 | High | |
| #601544 | DFNA3 | 604418 | 13q12 | GJB6 | Connexin 30 | Gap junction protein | Mid to high | ||
| #600994 | DFNA5 | 608798 | 7p15 |
ICERE-1/
DFNA5 |
ICERE-1 | Potential role in p53- regulated response to DNA damage in cochlea |
5–15 | High | |
| #600965 | DFNA6/ 14/38 |
606201 | 4p16.1 | WFS1 | Wolframin | Integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum |
5–15 | Low | |
| #601543 | DFNA8/12 | 602574 | 11q22-q24 | TECTA | α-Tectorin | Structural component of tectorial membrane |
Variable: prelingual/ postlingual to 9–19 |
Mid (mid to high) |
|
| #601369 | DFNA9 | 603196 | 14q12-q13 | COCH | Cochlin | Extracellular matrix protein |
20–30 | High | Meniere-like symptoms |
| #601316 | DFNA10 | 603550 | 6q23 | EYA4 | EYA4 | Transcriptional activator | 20–60 | All | |
| #601317 | DFNA11 | 276903 | 11q13.5 | MYO7A | Myosin VIIA | Unconventional motor molecule |
All or low | Symptoms of vestibular dysfunction |
|
| #601868 | DFNA13 | 120290 | 6p21.3 | COL11A2 | Collagen 11A2 | Structural molecule | 20–40 | Mid (cookie-bite) | |
| #602459 | DFNA15 | 602460 | 5q31 | POU4F3 | POU4F3 | Transcription factor | 20–40 (with variability to puberty) |
All | |
| #603622 | DFNA17 | 160775 | 22q11.2 | MYH9 | MYH9 | Nonmuscle myosin heavy chain |
5–10 | High | Cochleo-saccular degeneration |
| #606346 | DFNA22 | 600970 | 6q13 | MYO6 | Myosin VI | Unconventional motor molecule |
8–10 | All | |
| #606705 | DFNA36 | 606706 | 9q13-q21 | TMC1 | TMC1 | Transmembrane protein | 0–10 or 30–50 |
High to all | |
| #220290 | DFNB1 | 121011 | 13q11-q12 | GJB2 | Connexin 26 | Gap junction protein | Prelingual | All | |
| #220290 | DFNB1 | 604418 | 13q12 | GJB6 | Connexin 30 | Gap junction protein | Prelingual | All | |
| #600060 | DFNB2 | 276903 | 11q13.5 | MYO7A | Myosin VIIA | Unconventional motor molecule |
Prelingual | All | Symptoms of vestibular dysfunction |
| #600316 | DFNB3 | 602666 | 17p11.2 | MYO15A | Myosin XVA | Unconventional motor molecule |
Prelingual | All | |
| #600791 | DFNB4 (EVA) | 605646 | 7q13 | SLC26A4 | Pendrin | Anion transporter | Prelingual | High to all | Dilated vestibular aqueduct |
| #600974 | DFNB7/11 | 606706 | 9q13-q21 | TMC1 | TMC1 | Transmembrane protein | Prelingual | All | |
| #601072 | DFNB8 | 605511 | 21q22.3 | TMPRSS3 | TMPRSS3 | Serine protease | Prelingual or 10–12 |
All | |
| #601071 | DFNB9 | 603681 | 2p23-p22 | OTOF | Otoferlin | Synaptic vesicle component |
Prelingual | All | |
| #605316 | DFNB10 | 605511 | 21q22.3 | TMPRSS3 | TMPRSS3 | Serine protease | Congenital | ||
| #601386 | DFNB12 | 605516 | 10q21-q22, 3p26-p25 |
CDH23 | Cadherin 23 | Cell adhesion protein | Prelingual | All | |
| #603720 | DFNB16 | 606440 | 15q15 | STRC | Stereocilin | Stereocilia protein | Prelingual or 3–5 |
All | |
| #602092 | DFNB18 | 605242 | 11p15.1 | USH1C | Harmonin | PDZ domain protein | Prelingual | All | |
| #603629 | DFNB21 | 602574 | 11q22-q24 | TECTA | α-Tectorin | Structural component of tectorial membrane |
Prelingual | All | |
| #607039 | DFNB22 | 607038 | 16p12.2 | OTOA | Otoancorin | Anchoring protein between acellular gels and nonsensory cells |
Prelingual | All | |
| 605608 | DFNB29 | 605608 | 21q22.3 | CLDN14 | Claudin 14 | Tight junction protein | Prelingual | All | |
| #607821 | DFNB37 | 600970 | 6q13 | MYO6 | Myosin VI | Unconventional motor molecule |
Prelingual | All | Symptoms of vestibular dysfunction |
| 304500 | DFNX1 | N/A | Xq22 | N/A | N/A | N/A | Variable | All | |
| 304400 | DFNX2 | 300039 | Xq21.1 | POU3F4 | POU3F4 | POU domain transcription factor |
Prelingual | All | |
| 300030 | DFNX3 | 300377(?) | Xp21.2 | DMD (?) | Dystrophin (?) | Membrane structure protein |
Congenital | All | |
| 300066 | DFNX4 | N/A | Xp22 | N/A | N/A | N/A | Postlingual | High to all | |
| 300614 | DFNX5 | N/A | Xq23-27.3 | N/A | N/A | N/A | Postlingual | Low to all | |
| 40043 | DFNY1 | N/A | Y | N/A | N/A | N/A | 7–27 years | All | |