Table 3 Summary of all known EYA4 variants and their hearing loss phenotypes

Splicing

c.84-2A > G

Intron 3

Chinese

Indian

N/A

N/A

N/A

Chen et al. 2016 [36]

Panigrahi et al. [37]

Missense

c.152C > T

Exon 4

p.Ser51Phe

America

N/A

N/A

N/A

Sloan-Heggen et al. [38]

Nonsense

c.160G > T

Exon 4

p.Glu54*

Spanish

42 years

Mild

MF/flat

Morín et al. [13]

Frameshift

c.222_223del

Exon 5

p.Val75Phefs*32

Japanese

61 years

Mild to moderate

HF/LF

Shinagawa et al. [9]

Frameshift

c.464delC

Exon 8

p.Pro155Glnfs*43

Swedish Dutch

N.A Childhood

N.A

Moderate

N.A

MF/HF

Neveling et al. [39]

Van Beelen et al. [40]

Frameshift

c.498del

Exon 8

p.Thr167Leufs*31

Japanese

13 years

Mild

LF

Shinagawa et al. [9]

Missense

c.511G > C

Exon 8

p.Gly171Arg

Chinese

6–50 years

Mild to severe

HF/flat

Liu [15]

Nonsense

c.517C > T

Exon 8

p.Gln173*

Japanese

48 years

Moderate

Flat

Shinagawa et al. [9]

Missense

c.543C > G

Exon 8

p.Tyr181Ter

Chinese

Second to the fourth decade

Severe to profound

Flat

Mi et al. [32]

Frameshift

c.579_580insTACC

Exon 8

p.Asp194Tyrfs*52

Swedish

4–40 years

Mild to profound

N/A

Frykholm et al. [41]

c.580 + 1G > A

Intron 8

Japanese

45 years

Moderate

Flat

Shinagawa et al. [9]

Frameshift

c.614dupA

Exon 9

p.Glu205Argfs*40

Chinese

20–40 years

Moderate to profound

HF/flat

Huang et al. [42]

Frameshift

c.781del

Exon 10

p.Thr261Argfs*34

Spanish

26–44 years

Mild to moderate

Gently downsloping

Morín et al. [13]

Missense

c.804G > C

Exon 10

p.Gln268His

Slovak

10–40 years

Moderate

Gently downsloping

Varga et al. [43]

Nonsense

c.863C > A

Exon 11

p.Ser288*

Korean Korean

N.A

N.A

Moderate

Moderate to severe

Reverse U-shaped

Flat

Baek et al. [44]

Kim et al. [10]

Missense

c.866C > T

Exon 11

p.Thr289Met

American

N.A

N.A

N.A

Miszalski-Jamka et al. [45]

Frameshift

c.910del

Exon 11

p.Ser305Leufs*15

Japanese

30 years

Severe

Flat

Shinagawa et al. [9]

Missense

c. 978C > G

Exon 12

p.Phe326Leu

Korean

N.A

Moderate

Down sloping

Choi et al. [46]

Nonsense

c.988C > T

Exon 12

p.Gln330*

Japanese

16 years

Moderate

Flat

Shinagawa et al. [9]

Frameshift

c.1026_1027dupAA

Exon 12

p.Thr343Lysfs*62

American

N.A

Moderate to profound

Flat/Gently sloping

Wayne et al. [12]

Frameshift

c.1048_1049dupAA

Exon 12

p.Arg352Profs*53

American

N.A

Moderate to severe

MF/HF

Makishima et al. [47]

Missense

c.1078C > A

Exon 12

p.Pro360Thr

Spanish

44 years

Mild to moderate

Gently downsloping

Morín et al. [13]

Missense

c.1107G > T

Exon 12

p.Glu369Asp

Spanish

10–11 years

Moderate to severe

Gently downsloping

Morín et al. [13]

Missense

c.1109G > A

Exon 13

p.Arg370His

Philippines

N.A

N.A

N.A

Truong et al. 2019 [48]

Missense

c.1109G > C

Exon 13

p.Arg370Pro

Japanese

30 years

Mild to moderate

MF

Shinagawa et al. [9]

Missense

c.1109G > C

Exon 13

p.Val371Met

Belgium

N.A

N.A

N.A

Sommen et al. [49]

Frameshift

c.1115_1118dup TTGT

Exon 13

p.Trp374Cysfs*6

Hungarian

N.A

N.A

N.A

Pfister et al. [50]

Missense

c.1122G > T

Exon 13

p.Trp374Cys

Australian

10–25 years

Mild to severe

Gently downsloping

Morín et al. [13]

Missense

c.1154C > T

Exon 13

p.Ser385Leu

Italian

N.A

Mild to profound

MF

Cesca et al. [51]

Nonsense

c.1177C > T

Exon 13

p.Gln393*

Korean

Japanese

N.A

26 years

moderate

HF

Flat

Kim [10]

Shinagawa et al. [9]

Frameshift

c.1194del

Exon 14

p.Met401Trpfs*3

Korean

N.A

Moderate

Down sloping

Choi et al. [46]

Missense

c.1216G > C

Exon 14

p.Gly406Arg

Japanese

5 years

Moderate

Flat

Shinagawa et al. [9]

Missense

c.1223G > A

Exon 14

p.Arg408His

America

N.A

N.A

N.A

Miszalski-Jamka et al. [45]

Missense

c.1281G > A

Exon 14

p.Glu427Glu

Spanish

26 years

Moderate to profound

Flat

Morín et al. [13]

Splicing

c.1282-12T > A

Intron 14

Australian

N.A

Mild to profound

Flat

Hildebrand et al. [52]

Splicing

c.1282-1G > A

Intron 14

Spanish

12 years

Mild to moderate

MF/Flat

Morín et al. [13]

Missense

c.1301T > A

Exon 15

p.Ile434Lys

Chinese

8–38 years

Mild to severe

MF/flat

Tan et al. [53]

Splicing

c.1341-19T > A

Intron 15

Germany

N.A

N.A

N.A

Vona et al. [54]

Nonsense

c.1601C > G

Exon 17

p.Ser534*

Spanish

3–16 years

Moderate to severe

MF/Flat

Morín et al. [13]

Missense

c.1643C > G

Exon 18

p.Thr548Arg

Chinese

17–40 years

Mild to profound

N.A

Sun et al. [11]

Missense

c.1663G > C

Exon 18

p.Ala555Pro

Japanese

25 years

Moderate

N.A

Shinagawa et al. [9]

Splicing

c.1739-1G > A

Intron 18

America

50 years

N.A

N.A

Cirino et al. [55]

Nonsense

c.1759C > T

Exon 19

p.Arg587*

Belgian

6–40 years

Mild to moderate

N.A

Wayne et al. [12]

Frameshift

c.1790del

Exon 19

p.Val597Glyfs*4

Japanese

35 years

Moderate

Flat

Iwasa et al. [56]

Missense

c.1810G > T

Exon 19

p.Gly604Cys

Swedish Dutch

N.A

N.A

N.A

Neveling et al. [39]

Van Beelen et al. [40]

Nonsense

c.1834A > T

Exon 19

p.Lys612*

Chinese

27 years

Moderate

Gently downsloping

Hu et al. [16]

Missense

c.1855T > G

Exon 20

p.Trp619Gly

Chinese

N.A

N.A

N.A

Xiao et al. [57]

CNV

Deletion 7689 bp

(Ex7 to Ex11)

Japanese

25 years

Moderate to severe

LF/HF

Shinagawa et al. [9]

CNV

Deletion 9.5 Mb

(Ex4 to Ex 20)

Japanese

13 years

Severe

LF/HF

Shinagawa et al. [9]

CNV

Deletion 2747 bp

(Ex15 to Ex17)

Spanish

8 years

Moderate

Flat

Morín et al. [13]

CNV

Deletion 9 Mb at 6q23.1–24.1

(Ex4–20)

p.Asp194Glyfs*30

Polish

N.A

N.A

N.A

Dutrannoy et al. [30]

CNV

Deletion 4846 pb incl. intron 9, exon 10 and partial intron 10 c.581_804del

(In9, Ex10, part of In10)

N.A

N.A

N.A

Schönberger et al. [34]

CNV

Deletion 10.4 Mb promoter and exon 1,2 (Ex1–2)

Japanese

20-month-old

Moderate to severe

MF/flat

Abe et al. [31]

CNV

Deletion 3.7 MB in 6q23.1q23.2

(Ex1–20)

Italian

12 years

N.A

N.A

Gana et al. [58]

CNV

Deletion 12,835 bp (Ex6–10)

Japanese

23 years

Mild to sereve

LF/HF/Flat

Ishino et al. [14]

CNV

Deletion 17.4 kb and 10 bp insertion (Ex8–11)

Chinese

26–42 years

Moderate–severe

Flat

This work