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. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: Int J Audiol. 2019 Jul 2;58(12):834–850. doi: 10.1080/14992027.2019.1632499

Table 3: Genes Associated with Pre-lingual Deafness of Delayed Diagnosis.

This comprehensive table summarizes genes associated with pre-lingual HL, which have been published in the literature.

Gene Gene Function Common Mutation(s) Inheritance Ethnic Group Description of Phenotype (onset) Carrier Frequency or Prevalence Reference
GJB2 Gap junction in cochlea involved in ion recycling c.109G>A (p.V37I) AR Chinese, Japanese Mild to severe-profound, bilateral. Onset in first decade of life. Control allele frequency 6.2% Chen et al. 2014; Li et al. 2012; Minami et al. 2013
c.235delC AR Japanese Mild to severe-profound. Onset between 4 months and 6 years Minami et al. 2013
c.512ins4 AR Japanese Profound-severe. Onset before 1 year. Minami et al. 2013
p.Y136X-p.G45E AR Japanese Moderate-severe. Onset before 2 years Minami et al. 2013
c.176–191del16 AR Japanese Moderate. Onset at 3 years. Minami et al. 2013
p.R143W AR Japanese Moderate-profound. Onset before 2 years. Minami et al. 2013
SLC17A8 Encodes a vesicular glutamate transporter in inner hair cells c.616dupA (p.M206Nfs*4) AD Korean Bilateral, severe Novel mutation Ryu et al. 2016
c.632C>T (p.A211V) AD American, Czech and German descent Progressive. Onset beginning at age 20. Not found in controls Ruel et al. 2008
SLC26A4 Transports chloride and iodine to maintain pH of endolymph p.1652insT AR Japanese Age of onset 1–2 years. Miyagawa et al. 2014
p.H723R AR Japanese Age of onset 1–10 years. Miyagawa et al. 2014
p.T527P AR Japanese Age of onset 2–3 years. Miyagawa et al. 2014
p. M147V AR Japanese Age of onset 2–3 years. Miyagawa et al. 2014
p.919–2A>G AR Japanese Age of onset 1–14 years. Miyagawa et al. 2014
p.1707+5G>A AR Japanese Age of onset 1–4 years. Miyagawa et al. 2014
KCNQ4 Voltage gated potassium channel c.211delC (P.Q71fs) AD Japanese Mild-severe, high frequency, progressive. Patients presented at 7 and 13 years Sakuma et al.
c.664_681del AD Korean Bilateral, symmetric, mild to profound, progressive. Onset beginning at 4 years. Novel mutation Baek et al. 2011
MYO15A Unconventional motor molecule c.3756+1G>A; c.4660G>A (p.A1554T) AR Japanese Profound, progressive. Presented at age 5. Sakuma et al.
c.9478C>T; 1179_1185insC AR Japanese Progressive. Detected on NBHS Miyagawa et al. 2013
LOXHD1 c.G3076G>T (p.V1026F); c.4375+1G>T Sporadic Japanese Profound, downsloping, stable. Presented at age 3. Sakuma et al.
USH2A c.57_58del (p.M14fs); c.9079G4T (p.E3027X) Sporadic Japanese Moderate, downsloping, progressive. Presented at age 10. Sakuma et al.
WSF1 Membrane glycoprotein that localizes to endoplasmic reticulum c.2508G>T (p.K836N) AD Japanese Moderate, U-shape, stable. Presented at age 5. Sakuma et al.
STRC Stereocilia protein CNV AR Japanese Mild-moderate, progressive. Detected in early childhood 1.1%−2.5% Moteki et al.
ADCY1 Adenylate cyclase 1 of hair cells c.3112C>T (p.Arg1038*) AR Pakistani Highly variable: Bilateral symmetric mild-moderate; asymmetric profound; mixed. Novel mutation Santos-cortez et al. 2014
TBC1D24 GTPase-activating protein expressed in the cochlea c.208G>T (p.Asp70Tyr); c.878G>C (p.Arg293Pro) AR Pakistani Prelingual; Severe-profound, downsloping or flat Not found in controls Rehman et al. 2014
c.533C>T (p.Ser178Leu) AD European, Chinese Progressive, downsloping. Age of onset 3rd decade Not found in controls Azaiez et al. 2014; Zhang et al. 2014
DCDC2 Kinocilium of sensory hair cells and cilia of supporting cells c.1271A>C, p.Gln424Pro AR Tunisian Congenital; Severe-profound Not found in controls Grati et al. 2015
NARS2 Mitochondrial asparaginyl-tRNAsynthetase c.637G>T; p.Val213Phe AR Pakistani Bilateral, severe-profound Not found in controls Simon et al. 2015
MET Receptor tyrosine kinase c.2521T>G (p.F841V) AR Pakistani Severe-profound. Hearing loss at or before 2 years of age Not found in controls Mujtaba et al. 2015
TMEM132E Mechanotransduction of hair cells c.1259G>A, p.Arg420Gln AR Chinese Pre-lingual; Bilateral, Severe-profound Not found in controls Li et al. 2015
GRXCR2 Devlopment of stereocilia bundles c.714dupT (p.G239WfsX74) AR Pakistani Moderate to severe, progressive. Onset at 2 years of age. Not found in controls Imtiaz et al. 2014
EPS8 EGFR pathway substrate 8, expressed in hair bundle in cochlea c.88C > T (p.Gln30*) AR Algerian Congenital; Profound; Not found in controls Behlouli et al. 2014
CLIC5 Vestibular function c.96T4A (p.(Cys32Ter) AR Turkish Pre-lingual; Progrssive from mild to severe before second decade, profound. Onset within first 2 years. Not found in controls Seco et al. 2014
FAM65B Plasma membrane associated protein of hair cell stereocilia c.102–1G>A AR Turkish Pre-lingual; Symmetric, profound, stable Not found in controls Diaz-Horta et al. 2014
OSBPL2 Intracellular lipid receptor c.153_154delC (p.Gln53Argfs*100) AD Chinese Bilateral, progressive. Age of onset 5–32 years. Not found in controls Xing et al. 2014
c.141_142delTG (p.Arg50Alafs*103) AD German Bilateral, mild to profound, progressive. Onset betwen 10–30 years. Not found in controls Thoenes et al. 2015
HOMER2 Intracellular calcium homeostasis and cytoskletal organization p.Arg185Pro AD European Normal downsloping to moderate-severe. Post lingual, progressive Azaiez et al. 2015
COL4A6 Collagen type IV c.1771G>A, p.Gly591Ser X linked Hungarian Congenital; severe in males, mild-moderate in female carriers Rost et al. 2014
MT-TL1 m.3243A>G Mitochondrial Japanese Onset in childhood, or 3rd and 4th decade. 6.57–16.3 per 100000 Kato et al. 2010
12s rRNA m.1555A>G Mitochondrial Polish Onset within first 2 decades. 0.40% Rydzanicz et al. 2010
m.669T>C Mitochondrial Polish Onset between 5–54 years. 0.20% Rydzanicz et al. 2010
m.827A>G Mitochondrial Polish Onset at less than 1 year. 0.20% Rydzanicz et al. 2010
m.961 delT+C(n) Mitochondrial Polish Onset at 20 years. 0% Rydzanicz et al. 2010
m.988G>A Mitochondrial Polish Onset within first 3 years of life. One outlier at 41 years. 0.20% Rydzanicz et al. 2010
m.1453A>G Mitochondrial Polish Onset in early childhood. 0% Rydzanicz et al. 2010
COCH Extracellular matrix protein c.1196_1213del AR Bilateral, progressive late onset with tinnitus.Onset in 20s. Gallant et al.2013
TECTA Structural component of tectorial membrane c.1471C>T (p.R491C); c.596delT AR Japanese Progressive hearing loss. Detected on NBHS Miyagawa et al. 2013
9.6kb deletion (p.984X) AR Iranian Pre-lingual; Moderate-severe Meyer et al. 2007
266delT (p.122X) AR Iranian Pre-lingual; Moderate-severe Meyer et al. 2007
c.5211C > A (p.Y1737X) AR Iranian Pre-lingual; Moderate-severe Meyer et al. 2007
c.6203–6218del (p.2110X) AR Iranian Pre-lingual; Moderate-severe Alasti et al.2008
BDP1 Subunit of RNA polymerase III transcription initiation factor IIIB c.7873 T>G (p.*2625Gluext*11) AR Qatari Pre-lingual; Moderate-severe, downsloping, progressive. Onset between 2 and 4 years old. Girotto et al. 2013
CABP2 Calcium binding protein 2 c.637+1G>T AR Iranian Pre-lingual; Moderate-severe, flat to shallow U shaped audiogram Schrauwen et al. 2012
ELMOD3 Engulfment and cell motility family c.794T>C; p.Leu265Ser AR Pakistani Pre-lingual; Severe-profound, mixed Not found in controls Jaworek et al. 2013
GPSM2 G-protein signaling modulator 2 p.R127X AR Palastinian Pre-lingual; Severe-profound, down sloping Not found in controls Walsh et al. 2010
c.1684C>T (p.Q562X) AR Turkish Pre-lingual; Bilateral, Severe-profound Not found in controls Yariz et al. 2012
KARS Lysyl-tRNA synthetase c.1129G>A (p.Asp377Asn) AR Pakistani Pre-lingual; Bilateral, symmetric severe moderate-severe or severe-profound, stable Not found in controls Basit et al. 2011; Santos-Cortez et al. 2013.
OTOGL Otogelin-like protein in innr ear c.1430 delT (p.Val477Glufs∗25) AR Turkish Pre-lingual; symmetric, moderate, stable Yariz et al. 2012
c.547C>T (p.Arg183∗); c.5238+5G>A AR Dutch Pre-lingual with diagnosis at age 3, or congenital. Moderate, stable. Yariz et al. 2012
c.1558C>T (p.Gln520*); c.2773C>T (p.Arg925*) AR French Mild. Diagnosed at 5 years. Bonnet et al. 2013
TPRN Taperin; possible role in actin dynamics c.1347delG (p.Thr450LeufsX32) AR Dutch Pre-lingual; Severe-profound, downsloping or flat; diagnosis within first 4 years. Not found in controls Li et al. 2010
c.42_52del (p.Gly15AlafsX150) AR Moroccan; Pakistani Congenital or pre-lingual; Severe-profound, progressive Not found in controls Li et al. 2010; Rehman et al. 2010
CEACAM16 Carcinoembryonic antigen related cell adhesion molecule in outer hair cells c.418A>C (p.T140P) AD American Bilateral, moderate, progressive. Onsetin early adolescence Not found in controls Zheng et al. 2011
c.505G4A (p.G169R) AD Chinese Severe-profound, progressive Onset in first 3 decades. Not found in controls Wang et al. 2015
P2RX2 Ligand-gated ion channel, purinergic receptor c.178G>T (p.V60L) AD Chinese Bilateral, symmetric, moderate-severe, progressive. Onset between 12 to 20 years. <0.001 in Chinese, <0.0001 in mix-ed ancestry Yan et al.2013
c.1057G>C (p.Gly353Arg) AD Italian Bilateral, mild to profound, progressive. Age of onset 2nd decade. Not found in controls Faletra et al.2014
TNC Tenacin-C in extracellular matrix, basilar membrane, and cochlea c.5317G>A (p.V1773M) AD Chinese Bilateral, symmetric, severe, progressive. Onset from 8 to 30 years. <0.0005 Zhao et al.2013
TSPEAR Thrombospondin-type lamin G domain and EAR repeats c.1726G>T1c.1728delC (p.V576LfsX37) AR Iranian Congenital; Bilateral, profound Not found in controls Delmaghani et al. 2012
SMPX Small muscle protein c.214G>T (p.Glu72X) X linked Dutch Bilateral, progressive. Onset in males 2–10 years, and in females 3–48 years. Not found in controls Schraders et al. 2011
c.109G>T (p.Glu37X) X linked German Moderate, progressive. Onset in males 3–7 years, and in females 10–15 years Huebner et al. 2011
c.175G>T (p.Gly59X) X linked Spanish Bilateral, symmetric, severe-profound, progressive. Onset in males 5–7 years, and in females 4th decade. Huebner et al. 2011
TMPRSS3 Type II transmembrane serine protease c.607C>T (p.Q203X); c1159G>A (p.A387T) AR Japanese Progressive. Onset in childhood. Miyagawa et al. 2013
ACTG1 Actin isoform in auditory hair cells c.895C.G (p.L299V) AD Japanese Bilateral, progressive. Onset at age 20. Miyagawa et al. 2013
CLDN14 Component of tight junctions c.488C>T (p.Ala163Val) AR Canadian Pre-lingual, onset at 3 years.Bilateral, symmetrical, severe, progressive. 1% Pater et al. 2017
DIAPH1 Regulation of actin polymerization in hair cells of inner ear Onset 0–20 years.