AUTHOR CONTRIBUTIONS
Conceptualization: AC, YF, JL. Data curation: AC, CH, XP. Formal analysis: AC, XP, JS. Funding acquisition: YF, CH, LM (Lu Ma), JS, AC. Methodology: AC, XP, SZ, MQ, SM, YC. Project administration: JL, LM (Lingyun Mei), LM (Lu Ma). Visualization: AC, YB, XL, ZF, DH. Writing–original draft: AC, JL, LM (Lu Ma). Writing–review & editing: YF, CH.
Location (exon/IVS) | Nucleotide change | ACMG classification | Phenotype (B, D, P, R) | CADD Phred | Severity of HL | FH | HL type | Ethnicity | Database | Study |
---|---|---|---|---|---|---|---|---|---|---|
Exon 6 | c.418 G>A | Pathogenic | B, D, P | 33 | Mild-profound | S | C, M | Korean | DVD | Kim et al. (2014) [5] |
IVS 6 | c.418+1 G>C | Pathogenic | B, D, R | 34 | NA | S | S | Japanese | HGMD, DVD | Unzaki et al. (2018) [3] |
IVS 7 | c.557-2 A>G | Pathogenic | B, P, D | 34 | Moderate | NA | C | Canadians | HGMD, DVD | Stockley et al. (2009) [27] |
Exon 8 | c.638 A>T | Pathogenic | B, D, P, R | 33 | NA | S | NA | American | DVD | Orten et al. (2008) [28] |
Exon 8 | c.639 G>C | Pathogenic | NA | 36 | NA | NA | NA | American | DVD | Orten et al. (2008) [28] |
IVS 8 | c.639+1 G>C | Pathogenic | B, D, P | 34 | NA | F | NA | American | HGMD, DVD | Orten et al. (2008) [28] |
IVS 8 | c.639+2 delA | Pathogenic | B, D, P | 32 | NA | F | NA | American | HGMD, DVD | Orten et al. (2008) [28] |
IVS 8 | c.640-15 G>A | Pathogenic | B, D, P, R | 22.8 | NA | F | NA | American | HGMD | Orten et al. (2008) [28] |
Exon 9+IVS 8 | c.640-15_698 del GAGC…AACC | Pathogenic | NA | NA | NA | F | NA | American | DVD | Vervoort et al. (2002) [29] |
Exon9 | c.826 G>T | Pathogenic | D (1/3), P (2/3), R (1/3) | 62 | NA | F | NA | American | DVD | Clarke et al. (2006) [30] |
Exon 10 | c.965 A>G | Pathogenic | D (4/4), P (4/4), R (NA) | 33 | Severe | F | M | Korean | DVD | Song et al. (2013) [11] |
IVS 10 | c.966+1 G>C | Pathogenic | B, D | 34 | NA | S | NA | American | DVD | Mann et al. (2019) [31] |
IVS 10 | c.966+5 G>A | Pathogenic | B (2/3), D (3/3), P (2/3), R (3/3) | 18.45 | Mild-moderate | F | M | Canadians | HGMD, DVD | Stockley et al. (2009) [27] |
IVS 10 | c.966_966+14 del TGGCTATGACGTACC | Pathogenic | B, D, P | 32 | NA | S | NA | French | DVD | Krug et al. (2011) [32] |
IVS 10 | c.967-2 A>G | Pathogenic | B (3/4), D (3/4), P (4/4) | 34 | Mild-moderate | F | M | Korean | HGMD, DVD | Kwon et al. (2009) [33] |
IVS 10 | c.967-2 A>G | Pathogenic | B (3/3), D (3/3), P (3/3) | 34 | Profound | F | M | Chinese | DVD | Chen et al. (2019) [34] |
IVS 10 | c.967-1 G>A | Pathogenic | B, D, R | 35 | NA | F | NA | British | HGMD, DVD | Rickard et al. (2000) [35] |
Exon 11 | c.967 A>T | Pathogenic | B (3/6), D (6/6), P (5/6), R (1/6) | 41 | NA | F | C, M | Chinese | DVD | Wang et al. (2018) [36] |
IVS 11 | c.1050+1 G>C | Pathogenic | B (5/5), D (5/5), P (5/5), R (1/5) | 35 | Mild | F | C, M | Danes | HGMD, DVD | Henriksen et al. (2004) [37] |
IVS 11 | c.1050+1 G>T | Pathogenic | B, D, P, R | 35 | NA | F | NA | American | HGMD, DVD | Orten et al. (2008) [28] |
IVS 11 | c.1050+1 G>T | Pathogenic | B (1/2), D (2/2), P (2/2) | 35 | Moderate-profound | F | M | Chinese | HGMD, DVD | Feng et al. (2021) [17] |
Exon 11+IVS 11 | c.1048_1050+1 delCCCT | Pathogenic | B, D, P, R | 37 | NA | F | NA | American | DVD | Orten et al. (2008) [28] |
IVS 11 | c.1050+2 T>C | Pathogenic | D, P, R | 33 | NA | S | NA | Japanese | HGMD, DVD | Unzaki et al. (2018) [3] |
IVS 11 | c.1050+4 A>C | Pathogenic | B (4/4), D (4/4), P (4/4) | 17.23 | Moderate-profound | F | C, M | Chinese | - | This study |
IVS 11 | c.1051-12 T>G | Pathogenic | B, D, P | 25.7 | NA | F | NA | American | HGMD | Orten et al. (2008) [28] |
IVS 11 | c.1051-2 A>G | Pathogenic | B (2/3), D (3/3), P (3/3), R (1/3) | 34 | NA | F | NA | Japanese | HGMD, DVD | Okada et al. (2006) [38] |
IVS 11 | c.1051-1 G>C | Pathogenic | B, D, P | 34 | NA | F | NA | American | HGMD, DVD | Orten et al. (2008) [28] |
Exon12 | c.1051 G>T | Pathogenic | B (1/3), D (3/3), P (3/3), R (1/3) | 35 | NA | F | NA | Japanese | DVD | Okada et al. (2006) [38] |
Exon12 | c.1138 G>T | Pathogenic | B (1/2), D (1/2), P (2/2) | 46 | NA | F | NA | French | DVD | Krug et al. (2011) [32] |
Exon 12+IVS 12 | c.1138_1140+1 delinv GAAG | Pathogenic | B , D, P | 33 | NA | F | NA | American | DVD | Orten et al. (2008) [28] |
IVS 12 | c.1140+1 G>A | Pathogenic | B, D, P | 34 | Moderate-profound | S | M | Chinese | HGMD, DVD | Feng et al. (2021) [17] |
IVS 12 | c.1140+1 G>A | Pathogenic | D, P, R (NA) | 34 | Moderate | S | M | Korea | HGMD, DVD | Song et al. (2013) [11] |
IVS 12 | c.1140+1 G>T | Pathogenic | B, D, R | 35 | NA | F | NA | British | HGMD, DVD | Rickard et al. (2000) [35] |
IVS 12 | c.1141-1 G>A | Pathogenic | B (12/14), D (17/18), P (9/9), R (3/7) | 35 | Mild-severe | F | C, M, S | British | HGMD, DVD | Sanggaard et al. (2007) [39] |
IVS 13 | c.1199+1 G>C | Pathogenic | B, D, P, R | 34 | NA | S | NA | French | HGMD, DVD | Krug et al. (2011) [32] |
IVS 14 | c.1360+4 A>G | Pathogenic | B (19/21), D (21/21), P (18/21), R (4/7) | 22.9 | NA | F | M | British | HGMD, DVD | Sanggaard et al. (2007) [39] |
IVS 14 | c.1360+5 G>A | Pathogenic | B, D, R | 22.6 | Moderate-profound | S | C | Canadians | HGMD, DVD | Stockley et al. (2009) [27] |
Exon 15 | c.1475 G>C | Pathogenic | NA | 36 | NA | F | NA | American | DVD | Orten et al. (2008) [28] |
Exon 15 | c.1471_1474 dupGGGA | Pathogenic | B (2/2), D (2/2), P (2/2), R (2/2) | 33 | NA | F | NA | French | DVD | Krug et al. (2011) [32] |
Exon15 | c.1474 dupG | Pathogenic | B (3/3), D (3/3), R (2/3) | 36 | Severe | F | S | Korean | DVD | Kim et al. (2005) [40] |
IVS 15 | c.1475+1 G>C | Pathogenic | B, D, P, R | 34 | NA | S | C | Italians | HGMD, DVD | Gigante et al. (2013) [41] |
IVS 15 | c.1476-2 A>G | Pathogenic | B, D, P, R | 33 | NA | F | NA | American | HGMD | Orten et al. (2008) [28] |
Eon 16 | c.1597 G>A | Pathogenic | B, D ,P | 35 | Mild | S | C | Italians | DVD | Castiglione et al. (2014) [42] |
IVS 16 | c.1597+2 T>G | Pathogenic | NA | 34 | NA | S | NA | French | HGMD, DVD | Abdelhak et al. (1997) [43] |
IVS 16 | c.1598-2 A>C | Pathogenic | B, D, P | 33 | Moderate-profound | S | M | Korean | HGMD, DVD | Song et al. (2013) [11] |
IVS 16 | c.1598-1 G>A | Pathogenic | B, D, P, R | 34 | NA | S | NA | Japanese | HGMD, DVD | Okada et al. (2006) [38] |
Exon 17 | c.1697 dupA | Pathogenic | B, D, P, R | 36 | NA | F | NA | American | DVD | Orten et al. (2008) [28] |
Exon 17 | c.1695_1698 delCTTT | Pathogenic | B (7/8), D (8/8), P (7/8), R (3/8) | 39 | NA | F | NA | Netherlander | DVD | Kumar et al. (1998) [44] |
IVS 17 | c.1698+1 G>A | Pathogenic | B (2/2), D (2/2), P (2/2), R (2/2) | 34 | NA | F | NA | Spanish | HGMD, DVD | Rodriguez-Soriano et al. (2001) [45] |
IVS 17 | c.1698+1 G>T | Pathogenic | B, D, P | 35 | NA | F | NA | American | HGMD, DVD | Orten et al. (2008) [28] |
IVS 17 | c.1698+5 G>C | Pathogenic | NA | 21 | NA | S | NA | French | HGMD, DVD | Abdelhak et al. (1997) [43] |
The genetic spectrum of EYA1 pathogenic mutations in the splicing region. EYA1 canonical transcript NM_000503.6. For the phenotype column, the numerator represents the count of patients exhibiting the corresponding phenotype, and the denominator represents the total number of branchio-oto syndrome/branchio-oto-renal syndrome within the family.
HGMD, Human Gene Mutation Database; DVD, Deafness Variation Database; IVS, intervening sequence; ACMG, American College of Medical Genetics and Genomics; B, branchial anomalies; D, deafness; P, preauricular fistulae; R, renal anomalies; CADD, combined annotation dependent depletion; FH, family history; S, single patient; NA, not available; F, family; HL, hearing loss; C, conductive HL; M, mixed HL; SHL, sensorineural HL.