Table 3 Summary of Clinical features of previously discovered heterozygous variants in the WFS1 gene associated with DFNA6/14/38

Barrett et al.

2009

c.482G > A

p.Arg161Gln

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Goncavles et al.

2014 [44]

c.511G > A

p.Asp171Asn

< 40

moderate

LF

N/A

N/A

Tinnitus

N/A

N/A

N/A

Portuguese

Mohammadi-asl et al.

2021 [45]

c.559 C > T

p.Leu187Phe

12–26

severe to

profound

N/A

N/A

N/A

normal

N/A

N/A

Familiar

Iranian

Cryns et al.

2002 [46]

c.577 A > C

p.Lys193Gln

early

moderate

LF

N/A

N/A

N/A

N/A

N/A

De novo

European

Sloan-Heggen et al.

2016 [32]

c.799G > A

p.Asp267Asn

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iran

Kobayashi et al.

2018 [47]

c.908T > C

p.Leu303Pro

N/A

mild to

moderate

LF, MF

normal

normal

normal

N/A

N/A

Familiar

Japanese

Kobayashi et al.

2018

c.923 C > G

p.Ser308Cys

6–16

moderate

LF, MF

normal

normal

Vertigo

dizziness

N/A

N/A

Familiar

Japanese

Majander et al.

2022 [48]

c.937 C > T

p.His313Tyr

7

N/A

N/A

+

+

Learning

disability

N/A

N/A

De novo

British

Majander et al.

2022

c.968 A > G

p.His323Arg

4–30

 N/A

N/A

+

normal

normal

N/A

N/A

Familiar

British

Sloan-Heggen et al.

2015

c.1072G > A

p.Val358Met

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iran

Choi et al.

2013 [49]

c.1235T > C

p.Val412Ala

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Korean

Wang et al.

2019 [50]

c.1235T > C

p.Val412Ala

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

De novo

Chinese

Smith et al.

2004 [51]

c.1371G > T

p.Arg457Ser

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

In this study

c.1544_1545

insA

p.Phe515Leu

fsTer28

4

profound

HF

normal

normal

normal

56

Improved word and

sentence identification

De novo

Korean

Smith et al.

2004

c.1554G > A

p.Met518Ile

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Smith et al.

2004

c.1669 C > T

p.Leu557Phe

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Smith et al.

2004

c.1805 C > T

p.Ala602Val

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Kobayashi et al.

2018

c.1846G > T

p.Ala616Ser

19

moderate

HF

normal

normal

Vertigo

dizziness

N/A

N/A

Familiar

Japanese

Smith et al.

2004

c.1871T > C

p.Val624Ala

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Komatsu et al.

2002 [52]

c.1901 A > C

p.Lys634Thr

N/A

moderate

LF

normal

normal

normal

N/A

N/A

Familiar

Japanese

Wei et al.

2014 [53]

c.1957 C > T

p.Arg653Cys

N/A

mild to

severe

LF

normal

normal

normal

N/A

N/A

Familiar

Chinese

Kobayashi et al.

2018

c.1982 A > G

p.Asn661Ser

6

moderate

LF

normal

normal

normal

N/A

N/A

Familiar

Japanese

Tsai et al.

2007 [54]

c.2005T > C

p.Tyr669His

< 22

moderate

LF

normal

normal

normal

N/A

N/A

Familiar

Taiwanese

Liu et al.

2005 [55]

c.2016G > T

p.Leu672=

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

Chinese

Li et al.

2021 [56]

c.2020G > T

p.Gly674Trp

19–30

mild to

profound

LF, Flat

normal

normal

normal

N/A

N/A

Familiar

Chinese

Cryns et al.

2002

c.2021G > A

p.Gly674Glu

early

moderate to

severe

LF

N/A

N/A

N/A

N/A

N/A

Familiar

Netherland

Cryns et al.

2002

c.2021G > T

p.Gly674Val

early

moderate to

severe

LF

N/A

N/A

N/A

N/A

N/A

Familiar

Netherland

Kobayashi et al.

2018

c.2027G > A

p.Arg676His

6

severe

flat

normal

normal

normal

N/A

N/A

familiar

Japanese

Wei et al.

2014

c.2036_2038

delAGG

p.Glu689del

N/A

mild to

severe

LF

normal

normal

normal

N/A

N/A

Familiar

Chinese

Kobayashi et al.

2018

c.2045 A > G

p.Asn682Ser

4

moderate

LF

normal

normal

normal

N/A

N/A

De novo

Japanese

Rendtorff et al.

2011 [19]

c.2051 C > T

p.Ala684Val

early

severe to

profound

Flat, LF,

MF

+

normal

N/A

57

Considerably improved hearing

De novo

Familiar

Caucasian

Kobayashi et al.

2018

c.2051 C > T

p.Ala684Val

< 1

Profound

flat

normal

normal

normal

N/A

N/A

De novo

Japanese

Guan et al.

2020 [57]

c.2051 C > T

p.Ala684Val

2–9

Profound

Flat

normal

normal

normal

< 3

Language ability

improved

De novo

Chinese

Majander et al.

2022

c.2051 C > T

p.Ala684Val

4–60

 N/A

N/A

+/-

+/-

normal

N/A

N/A

Familiar

British

Lin et al.

2022 [58]

c.2051 C > T

p.Ala684Val

< 3

Profound

flat

N/A

N/A

normal

< 3

SRT 30dB,

WRS92% at

35dBHL,

CAP/SIR score 6/5

De novo

Taiwanese

In this study

c.2051 C > T

p.Ala684Val

< 1

Severe

flat

normal

normal

normal

29mo

CAP score 3

It-MAIS 38/40

De novo

Korean

In this study

c.2051 C > T

p.Ala684Val

< 1

Severe

flat

normal

normal

normal

Scheduled

N/A

De novo

Korean

Bramhall et al.

2008 [41]

c.2053G > C

p.Arg685Pro

< 4

moderate to

severe

LF

N/A

N/A

normal

N/A

N/A

Familiar

Caucasian

Sun et al.

2011 [24]

c.2086 C > T

p.His696Tyr

5–28

mild to

profound

LF, flat

normal

normal

Vertigo

dizziniss

N/A

N/A

Familiar

Chinese

Bespalova et al.

2001 [28]

c.2096 C > T

p.Thr699Met

< 25

moderate

LF

normal

normal

normal

N/A

N/A

N/A

Netherland

Sun et al.

2011

c.2108G > A

p.Arg703His

7–50

 N/A

LF

normal

normal

normal

N/A

N/A

De novo

Chinese

Kunz et al.

2003 [59]

c.2115G > C

p.Lys705Asn

< 1

moderate

LF

N/A

N/A

N/A

N/A

N/A

Familiar

Germans

Sloan-Heggen et al.

2016

c.2137_2139

delGAC

p.Asp713del

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iranian

Sloan-Heggen et al.

2016

c.2141 A > T

p.Asn714Ile

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iranian

Sivakumaran et al.

2004 [60]

c.2146G > A

p.Ala716Thr

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Bespalova et al.

2011

c.2146G > A

p.Ala716Thr

< 10

moderate to

severe

LF

normal

normal

normal

N/A

N/A

Familiar

Netherland

Irish

Kobayashi et al.

2018

c.2146G > A

p.Ala716Thr

< 15

moderate

LF

normal

normal

normal

N/A

N/A

familiar

Japanese

Majander et al.

2022

c.2161 A > T

p.Asn721Tyr

50

N/A

N/A

+

normal

nystagmus

N/A

N/A

Familiar

British

Kobayashi et al.

2018

c.2185G > A

p.Asp729Asn

< 28

moderate

HF

normal

normal

Vertigo

dizziness

N/A

N/A

Familiar

De novo

Japanese

Liu et al.

2005

c.2209G > A

p.Glu737Lys

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

Chinese

Sloan-Heggen et al.

2015

c.2282 C > T

p.Ala761Val

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iranian

Cryns et al.

2002

c.2300–2302

del

p.Iledel767

early

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

Netherland

Gurtler et al.

2005 [61]

c.2311G > C

p.Asp771His

5–20

moderate to

profound

LF

N/A

N/A

N/A

N/A

N/A

Familiar

Swiss

Bespalova et al.

2011

c.2335G > A

p.Val779Met

N/A

N/A

LF

normal

normal

normal

N/A

N/A

De novo

Americans

Rendtorff et al.

2011

c.2338G > C

p.Gly780Ser

congenital

profound

N/A

+

normal

N/A

N/A

N/A

Familiar

Caucasian

Kobayashi et al.

2018

c.2385G > C

p.Glu795Asp

6

moderate

LF, flat

normal

normal

normal

N/A

N/A

De novo

Japanese

Bai et al.

2014 [62]

c.2389G > A

p.Asp797Asn

1–17

severe to

profound

HF, flat

normal

normal

normal

N/A

N/A

familiar

Chinese

Cheng et al.

2018 [63]

c.2389G > A

p.Asp797Asn

1–65

mild to

profound

flat

normal

normal

normal

N/A

N/A

familiar

Chinese

Rendtorff et al.

2011

c.2389G > T

p.Asp797Tyr

3–4

severe to

profound

flat

+

normal

normal

N/A

N/A

Familiar

Caucasian

Majander et al.

2022

c.2390 A > T

p.Asp797Val

45

N/A

N/A

+

+

normal

N/A

N/A

Familiar

British

Deng et al.

2020 [64]

c.2407G > A

p.Val803Met

32–44

mild to

severe

HF

normal

+

Demyelinating disorders

N/A

N/A

Familiar

Chinese

Cryns et al.

2003 [65]

c.2419 A > C

p.Ser807Arg

early

N/A

LF

N/A

N/A

N/A

N/A

N/A

Familiar

British

Bespalova et al.

2011

c.2486T > C

p.Leu829Pro

6–32

moderate

LF

normal

normal

normal

N/A

N/A

N/A

Americans

Cryns et al.

2003

c.2492G > A

p.Gly831Asp

< 20

moderate

LF

N/A

N/A

normal

N/A

N/A

N/A

Americans

Fujikawa et al.

2010 [66]

c.2507 A > C

p.Lys836Thr

2–10

moderate

LF, MF

normal

normal

normal

N/A

N/A

Familiar

Japanese

Kobayashi et al.

2018

c.2507 A > C

p.Lys836Thr

6–28

mild to

severe

LF, MF

normal

normal

Vertigo

dizziness

N/A

N/A

familiar

Japanese

Hogewind et al.

2010 [67]

c.2508G > C

p.Lys836Asn

8–14

severe

flat

+

normal

normal

N/A

83% speech recognition

at 70dB SPL

Familiar

Netherland

Kobayashi et al.

2018

c.2508G > C

p.Lys836Asn

5–30

moderate to

profound

LF, flat

normal

normal

normal

N/A

N/A

familiar

Japanese

Mair et al.

2022 [68]

c.2508G > T

p.Lys836Asn

28

moderate to

severe

LF

+

normal

normal

N/A

N/A

familiar

Greek

Noguchi et al.

2005 [69]

c.2530G > A

p.Ala844Thr

< 6

moderate

LF

normal

normal

normal

N/A

N/A

familiar

Japanese

Gurtler et al.

2005

c.2576G > C

p.Arg859Pro

5–30

moderate

LF

N/A

N/A

N/A

N/A

N/A

Familiar

American

Hildebrand et al.

2008 [70]

c.2576G > C

p.Arg859Gln

2–45

mild to

moderate

LF

N/A

N/A

Parkinson disease

-

-

Familiar

American

Eiberg et al.

2006 [23]

c.2590G > A

p.Glu864Lys

4

moderate to

severe

LF, flat

+

+/-

normal

N/A

N/A

Familiar

Denmark

Fukuoka et al.

2007 [71]

c.2590G > A

p.Glu864Lys

4

moderate to

severe

LF

normal

normal

normal

N/A

N/A

familiar

Japanese

Kobayashi et al.

2018

2590G > A

p.Glu864Lys

3–7

moderate to

profound

LF, MF,

flat

+

normal

normal

N/A

N/A

familiar

Japanese

Guan et al.

2020

c.2590G > A

p.Glu864Lys

7

mild to

moderate

LF

normal

normal

normal

N/A

N/A

De novo

Chinese

Liu et al.

2005

c.2596G > A

p.Asp866Asn

N/A

N/A

LF

N/A

N/A

N/A

N/A

N/A

N/A

Chinese

Sloan-Heggen et al.

2016

c.2603G > A

p.Arg868His

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Iranian

Abu-El-Haija et al.

2021 [27]

c.2605_2616

del

p.Ser869_

His872del

3–4

 N/A

LF

+

+

normal

N/A

N/A

Familiar

Irish