Table 1.
Causative heterozygous variants were found in 20 index cases whose first clinical diagnosis was Waardenburg Syndrome (ND = not described, NA = not applicable, $ used to detect each variant).
| Index Cases | Gene | Clinical Phenotype | Variant | Prediction Protein | dbSNP | Technique $ | ClinVar | Deafness Variation Database | Mutation Taster | ACMG | Inheritance | Segregation Analysis | Previous Description of Variants |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LGH16 | MITF—NM_000248.4 | WS2 | c.33+5G>A | - | - | WES | ND | ND | NA | Uncertain significance (PM2, BP4, PP1) | Familial | Segregates in the family | ND |
| LGH3 | WS2 | c.258del | p.Glu87Argfs*19 | rs1576005420 | WES | Likely pathogenic | ND | Disease causing | Pathogenic (PVS1, PP5, PM2) | Sporadic | Inherited from unaffected mother | ND | |
| LGH18 | WS2 | c.607_608delAG | p.Arg203Alafs*10 | - | WES | ND | ND | Disease causing | Likely pathogenic (PVS1, PM2, PP1) | Familial | Segregates in the family | ND | |
| LGH26 | WS2 | c.610C>T | p.Gln204* | rs1559745185 | WES | Likely pathogenic | Likely pathogenic | Disease causing | Pathogenic (PVS1, PP5, PP3 PM2, PP1) | Familial | Segregates in the family | ND | |
| LGH14 | WS2 | Exon 5 and 6 deletion | - | - | qPCR/MLPA | ND | ND | NA | Pathogenic (PVS1) | Isolated | de novo | Same patient described in [22] as W14 | |
| LGH15 | WS2 | c.763C>T | p.Arg255* | rs1057517966 | WES | Pathogenic/Likely pathogenic | Pathogenic | Disease causing | Pathogenic (PVS1, PM2, PP3, PP5, PP1) | Familial | Segregates in the family | [38]—Patient P44 | |
| LGH12 | WS1 > WS2 | c.909G>A | p.Thr303= | rs1057521096 | WES | Pathogenic/Likely pathogenic | Pathogenic | Disease causing | Pathogenic (PP5, PM2, BP4, PS3) | Sporadic | NA | [37] | |
| LGH25 | WS2 | Exon 8 deletion | - | - | NGS panel | ND | ND | NA | Pathogenic (PVS1) | Familial | Segregates in the family | ND | |
| LGH5 | SOX10—NM_006941 | WS2 | c.12_13delinsAT | p.Gln5* | - | WES | ND | ND | Disease causing | Pathogenic (PVS1, PM2, PP3) | Sporadic | NA | [22]—Patient W6 |
| LGH10 | WS2 | c.271_275dup | p.Arg93Profs*18 | - | WES | ND | ND | Disease causing | Likely pathogenic (PVS1, PM2) | Sporadic | NA | ND | |
| LGH9 | EDNRB—NM_000115 | WS2 | Whole gene deletion | - | - | WES | NA | NA | NA | Pathogenic (PVS1_Stand-alone) | Sporadic | NA | ND |
| LGH11 | WS1 > WS2 | c.484-1G>A | - | - | NGS panel | ND | ND | Disease causing | Likely pathogenic (PVS1, PM2) | Sporadic | Inherited from unaffected mother | ND | |
| LGH17 | WS2 | c.898A>G | p.Met300Val | - | NGS panel | ND | ND | Disease causing | VUS (PM1, PM2) | Familial | Inherited from unaffected father | ND | |
| LGH24 | WS2 | c.1465-21_*1135del Exon 8 deletion |
- | - | NGS panel | ND | ND | NA | Pathogenic (PVS1, PP1) | Familial | Segregates in the family | ND | |
| LGH22 | PAX3—NM_181459 | WS1 | c.85_85+12delGGTAAGGGAGGGC | p.Val29Cysfs*81 | - | WES | ND | ND | Disease causing | Likely pathogenic (PVS1, PM2) | Familial | NA | ND |
| LGH13 | WS1 | c.115A>G | p.Asn39Asp | - | WES trio | ND | ND | Disease causing | Pathogenic (PP3, PM1, PM5, PM2, PS2) | Isolated | de novo | ND | |
| LGH21 | WS1 | c.896dup | p.Met299Ilefs*111 | - | WES | ND | ND | Disease causing | Pathogenic (PVS1, PM2, PP1) | Familial | Segregates in the family | ND | |
| LGH6 | WS1 | NC_000002.12 (NM_181459) c.958+104 (g.222221118_222221274dup) | ? | - | WES | ND | ND | NA | VUS (PM2, PM4, PP4) | Sporadic | NA | ND | |
| LGH23 | WS1 | c.1253del | p.Gly418Valfs*16 | rs778236891 | WES | ND | Unknown effect | Disease causing | Likely pathogenic (PVS1, PM2) | Familial | NA | ND | |
| LGH1 | ACTG1—NM_001614 | WS1 > BWS2 | c.277G>A | p.Glu93Lys | rs1568062529 | WES trio | Likely pathogenic | Likely pathogenic | Disease causing | Pathogenic (PS2, PM1, PM2, PP2, PP3, PP5) | Isolated | de novo | ND |