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Table 2 Clinical and genetic characteristics of cases with causative mutations

From: Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

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
  1. GenBank Accession and version numbers of the genes listed in the table: ACTG1 (NM_001614.3), BSND (NM_057176.2), CDH23 (NM_022124.5), CHD7 (NM_017780.3), COL4A5 (NM_000495.4), GATA3 (NM_001002295.1), MITF (NM_000248.3), MYO15A (NM_016239.3), P2RX2 (NM_174873.2), POU3F4 (NM_000307.4), PRPS1 (NM_002764.3), RDX (NM_002906.3), SLC26A4 (NM_000441.1), SOX10 (NM_006941.3), STRC (NM_153700.2), USH2A (NM_206933.2)
  2. aAmerican College of Medical Genetics and Genomics
  3. bYes: variants present in HGMD and/or Clinvar at the moment of clinical interpretation of the case; No: variants absent from both HGMD and ClinVar at the moment of clinical interpretation of the case