Table 4.
Characteristics of hearing cases with biallelic GJB2 variants involving p.Met34Thr or p.Val37Ilele, including homozygotes and compound heterozygotes with another pathogenic or likely pathogenic variant.
| Genotype | [Met34Thr]; [P/LP] | [Met34Thr]; [Met34Thr] | [Met34Thr]; [Val37Ile] | [Met34Thr]; [PTC] | [Val37Ile]; [P/LP] | [Val37Ile]; [Val37Ile] | [Val37Ile]; [PTC] | c.[35delG]; [35delG]1 |
|---|---|---|---|---|---|---|---|---|
| Total probands | 138 | 27 | 17 | 78 | 131 | 139 | 78 | 86 |
| Total with characterization2 | 183 | 28 | 17 | 86 | 127 | 150 | 91 | 86 |
| Age of Onset3 | 177 | 28 | 17 | 83 | 139 | 144 | 78 | 86 |
| Childhood (<18 years) | 155 (88%) | 23 (82%) | 16 (94%) | 72 (87%) | 113 (81%) | 120 (83%) | 50 (64%) | 84 (98%) |
| Laterality | 133 | 21 | 11 | 62 | 109 | 111 | 66 | 86 |
| Unilateral | 4 (3%) | 0 | 1 (9%) | 2 (3%) | 5 (5%) | 4 (4%) | 3 (5%) | 0 (0%) |
| Bilateral | 129 (97%) | 21 (100%) | 10 (99%) | 60 (97%) | 104 (95%) | 107 (96%) | 63 (95%) | 86 (100%) |
| Asymmetrical | 15 (12%) | 3 (27%) | 2 (20%) | 9 (15%) | 6 (6%) | 7 (7%) | 1 (2%) | 0 (0%) |
| Frequency ranges4 | 66 | 14 | 6 | 30 | 59 | 59 | 34 | 1 |
| High | 41 (62%) | 9 (64%) | 5 (83%) | 13 (43%) | 35 (59%) | 41 (69%) | 21 (62%) | 1 (100%) |
| Mid | 17 (26%) | 4 (29%) | 1 (17%) | 11 (37%) | 3 (5%) | 10 (17%) | 2 (6%) | 0 (0%) |
| Low | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 7 (12%) | 0 (0%) | 6 (18%) | 0 (0%) |
| Progression | 20 (11%) | 2 (7%) | 4 (24%) | 10 (12%) | 20 (16%) | 10 (7%) | 13 (14%) | 4 (4%) |
| Severity | 146 | 24 | 14 | 63 | 121 | 133 | 77 | 63 |
| Mild | 55 (38%) | 10 (42%) | 5 (36%) | 26 (41%) | 29 (24%) | 48 (36%) | 23 (30%) | 0 (0%) |
| Moderate | 67 (46%) | 8 (33%) | 7 (50%) | 29 (46%) | 55 (45%) | 52 (39%) | 34 (44%) | 7 (11%) |
| Mild+Moderate | 122 (84%) | 18 (75%) | 12 (86%) | 55 (87%) | 84 (69%) | 90 (75%) | 57 (74%) | 7 (11%) |
| Moderately severe | 12 (8%) | 3 (13%) | 2 (14%) | 3 (5%) | 20 (17%) | 12 (9%) | 9 (12%) | 9 (14%) |
| Severe | 4 (3%) | 0 (0%) | 0 (0%) | 3 (5%) | 16 (13%) | 20 (15%) | 10 (13%) | 9 (14%) |
| Profound | 8 (5%) | 3 (13%) | 0 (0%) | 2 (3%) | 1 (1%) | 1 (1%) | 1 (1%) | 38 (60%) |
| Statistics (OR[95%CI], p)5 | ||||||||
| [Met34Thr];[Val37Ile] | 0.86 [0.0–673], 0.97 | |||||||
| [Met34Thr];[PTC] | 0.76 [0.02–34], 0.89 | 0.88 [0.0–281], 0.97 | ||||||
| [Val37Ile];[Val37Ile] | 1.35 [0.04–49], 0.87 | 1.56 [0.0–432], 0.88 | 1.77 [0.47–7.7], 0.40 | |||||
| [Val37Ile];[PTC] | 1.36 [0.04–57], 0.87 | 1.00 [0.34–3.00], 0.88 | 1.78 [0.33–9.4], 0.50 | 1.00 [0.34–3.00], 0.99 | ||||
| c.[35delG];[35delG] | 79 [1.5–4210], 0.0315 | 91 [0.3–32548], 0.13 | 103 [11–902], <0.0001 | 58 [10–336], <0.0001 | 58 [7.7–438], <0.0001 |
Abbreviations: [P/LP], a pathogenic or likely pathogenic allele in GJB2; [PTC], an allele with a premature termination codon in GJB2; OR, odds ratio; CI, confidence interval; p, p value.
Data on c.35delG cases were from the Laboratory for Molecular Medicine only.
All information is not available for all individuals.
When age of onset was not available, age of testing was used as a surrogate.
Flat audiogram shapes that affect all frequency ranges are under-reported.
Odds ratio refers to the genotype in the column header more likely to be milder than that in the row header. Statistically significant differences in severity are in bold.