Table 2 Clinical and genetic characteristics of cases with causative mutations
Case ID | Pre-test phenotype | Pre-test suspected inheritance pattern | Time of deafness onset | Gene | Allele variants | Variant zygosity | ACMGa classification30 | Fulfilled ACMGa pathogenicity criteria30 | Present in HGMD and/or ClinVarb | Gene-associated phenotypes | Inheritance patterns of gene-associated phenotypes | Hidden syndrome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
OTO.008 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | MYO15A | c.8050 T > C p.(Tyr2684His) | Heterozygous | Likely pathogenic | PM2, PM3, PP1, PP3 | Yes | Non-syndromic sensorineural deafness (DFNB3) | AR | No |
c.8968-1G > T | Heterozygous | Pathogenic | PVS1, PM2, PP1 | No | ||||||||
OTO.001 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | STRC | Whole-gene deletion | Homozygous | Pathogenic | PVS1, PM2, PM3 | Yes | Non-syndromic sensorineural deafness (DFNB16) | AR | No |
OTO.033 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | STRC | Whole-gene deletion | Homozygous | Pathogenic | PVS1, PM2, PM3 | Yes | Non-syndromic sensorineural deafness (DFNB16) | AR | No |
OTO.050 | Bilateral non-syndromic sensorineural deafness | AD / AR | Childhood | RDX | Exon 2 deletion | Homozygous | Likely pathogenic | PVS1, PM2 | No | Non-syndromic sensorineural deafness (DFNB24) | AR | No |
OTO.009 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | BSND | c.23G > A p.(Arg8Gln) | Homozygous | Likely pathogenic | PM1, PM2, PM5, PP3 | No | Non-syndromic sensorineural deafness (DFNB73) / Bartter syndrome type IV | AR | Potential |
OTO.006 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | SLC26A4 | c.412G > T p.(Val138Phe) | Heterozygous | Pathogenic | PS3, PS(PM3), PP3 | Yes | Non-syndromic sensorineural deafness (DFNB4) / Pendred syndrome | AR | Potential |
c.1370A > T p.(Asn457Ile) | Heterozygous | Likely pathogenic | PM1, PM2, PM3, PP3 | Yes | ||||||||
OTO.018 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | CDH23 | c.4488G > C p.(Gln1496His) | Heterozygous | Pathogenic | PS3, PM2, PM3, PP1, PP3 | Yes | Non-syndromic sensorineural deafness (DFNB12) / Usher syndrome type 1D | AR | Potential |
Duplication of exons 11–15 | Heterozygous | Likely pathogenic | PM2, PM3, PM4 | No | ||||||||
OTO.004 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | USH2A | c.11864G > A p.(Trp3955*) | Homozygous | Pathogenic | PVS1, PS(PM3) | Yes | Usher syndrome type 2A | AR | Yes |
OTO.005 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | USH2A | c.1724G > A p.(Cys575Tyr) | Homozygous | Likely pathogenic | PS(PM3), PM2, PP3 | Yes | Usher syndrome type 2A | AR | Yes |
OTO.014 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | USH2A | c.1724G > A p.(Cys575Tyr) | Heterozygous | Likely pathogenic | PS(PM3), PM2,PP3 | Yes | Usher syndrome type 2A | AR | Yes |
c.1841–2A > G | Heterozygous | Pathogenic | PVS1, PS(PM3), PS3, PM2 | Yes | ||||||||
OTO.003 | Bilateral non-syndromic sensorineural deafness | AD | Childhood | P2RX2 | c.178G > T p.(Val60Leu) | Heterozygous | Likely pathogenic | PS3, PM2, PP1 | Yes | Non-syndromic sensorineural deafness (DFNA41) | AD | No |
OTO.043 | Bilateral non-syndromic sensorineural deafness | AD | Congenital | ACTG1 | c.434C > G p.(Ser145Cys) | Heterozygous | Likely pathogenic | PM1, PM2, PP2, PP3 | No | Non-syndromic sensorineural deafness (DFNA20/DFNA26) / Baraitser-Winter syndrome type 2 | AD | Potential |
OTO.023 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | ACTG1 | c.548G > A p.(Arg183Gln) | Heterozygous | Likely pathogenic | PS2, PP(PM2), PP2, PP3 | No | Non-syndromic sensorineural deafness (DFNA20/DFNA26) / Baraitser-Winter syndrome type 2 | AD (de novo) | Potential |
OTO.041 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | ACTG1 | c.848 T > C p.(Met283Thr) | Heterozygous | Likely pathogenic | PS2, PM2, PP2 | No | Non-syndromic sensorineural deafness (DFNA20/DFNA26) / Baraitser-Winter syndrome type 2 | AD (de novo) | Potential |
OTO.011 | Unilateral non-syndromic sensorineural deafness | AD | Childhood | MITF | c.909G > A p.(Thr303Thr) | Heterozygous | Likely pathogenic | PS3, PM2, PP1 | Yes | Waardenburg syndrome type 2A | AD | Yes |
OTO.051 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | SOX10 | c.135_154del p.(Ser45Argfs*15) | Heterozygous | Likely pathogenic | PVS1, PM2, PP3 | No | Waardenburg syndrome type 2E | AD | Yes |
OTO.019 | Bilateral non-syndromic sensorineural deafness | AR | Congenital | GATA3 | c.1018A > C p.(Asn340His) | Heterozygous | Likely pathogenic | PM1, PM2, PM6, PP2, PP3 | No | Barakat syndrome | AD (de novo) | Yes |
OTO.010 | CHARGE syndrome | AD | Congenital | CHD7 | c.235A > T p.(Lys79*) | Heterozygous | Pathogenic | PVS1, PM2, PP4 | No | CHARGE syndrome | AD | No |
OTO.015 | Bilateral non-syndromic sensorineural deafness | AR | Childhood | POU3F4 | c.692C > T p.(Thr231Ile) | Hemizygous (male) | Likely pathogenic | PM1, PM2, PP2, PP3 | No | Non-syndromic sensorineural deafness (DFNX2/DFN3) | XR | No |
OTO.016 | Bilateral non-syndromic sensorineural deafness | AD | Childhood | PRPS1 | c.826C > T p.(Pro276Ser) | Hemizygous (male) | Likely pathogenic | PM1, PM2, PP2, PP3 | No | Non-syndromic sensorineural deafness (DFNX1) | XD | No |
OTO.007 | Alport syndrome | AR | Childhood | COL4A5 | c.3525_3529dup p.(Pro1177Leufs*124) | Hemizygous (male) | Pathogenic | PVS1, PM2, PM6 | No | Alport syndrome | XD (de novo) | No |