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OTOF-Related Deafness

Synonyms: DFNB9, DFNB9 Nonsyndromic Hearing Loss

, PhD, , MD, and , MD.

Author Information

Initial Posting: ; Last Update: January 21, 2021.

Estimated reading time: 19 minutes

Summary

Clinical characteristics.

OTOF-related deafness is characterized by two phenotypes: prelingual nonsyndromic auditory neuropathy spectrum disorder (ANSD) and, less frequently, temperature-sensitive auditory neuropathy spectrum disorder (TS-ANSD).

  • OTOF-related ANSD is characterized by congenital or prelingual, typically severe-to-profound bilateral deafness without inner-ear anomalies on MRI or CT examination of the temporal bones. Otoacoustic emissions (OAEs) are present and auditory brain stem response is abnormal at birth. Newborn hearing screening testing of OAEs only will fail to detect this disorder in most individuals. OAEs may decrease or disappear with age in 20%-80% of individuals.
  • TS-ANSD typically presents with normal-to-moderate hearing loss (0-55 dB) at baseline body temperature. An elevation of body temperature (approximately 0.5°C or more) triggers significant bilateral hearing loss ranging from severe to profound, with resolution of hearing loss typically occurring within hours of a return to baseline body temperature.

Diagnosis/testing.

The diagnosis of OTOF-related deafness is established in a proband with suggestive findings and biallelic pathogenic variants in OTOF identified by molecular genetic testing.

Management.

Treatment of manifestations: Hearing aids should be fitted as soon as possible after hearing loss is identified. Consideration of cochlear implants (CIs) as soon as possible if hearing aids are not beneficial, as CIs have been shown to be effective for both phenotypes associated with OTOF-related deafness. Educational programs designed for individuals with hearing impairment should start as early as possible.

Prevention of primary manifestations: For individuals with TS-ANSD, prevent fevers and other activities/ambient conditions that would cause body temperature to rise; treat febrile episodes as quickly as possible.

Surveillance: Audiometry and speech discrimination testing every six months until age 18 years, then annually.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic sibs of a proband shortly after birth by molecular genetic testing for the pathogenic variants found in the proband so that appropriate early support and management can be provided to the child and family.

Genetic counseling.

OTOF-related deafness is inherited in an autosomal recessive manner. If both parents are known to be carriers, each sib of an individual with OTOF-related deafness has at conception a 25% chance of being deaf, a 50% chance of having normal hearing and being a carrier, and a 25% chance of having normal hearing and not being a carrier. Once the OTOF pathogenic variants have been identified in the family, carrier testing, prenatal testing, and preimplantation genetic testing for OTOF-related deafness are possible.

GeneReview Scope

OTOF-Related Deafness: Included Phenotypes 1
Primary designation used in this GeneReviewOther designations
Auditory neuropathy spectrum disorder (ANSD)
  • Auditory synaptopathy
  • Auditory dyssynchrony
Temperature-sensitive auditory neuropathy spectrum disorder (TS-ANSD)
  • Temperature-sensitive nonsyndromic auditory neuropathy
  • Temperature-sensitive nonsyndromic auditory synaptopathy
  • Temperature-sensitive nonsyndromic auditory dyssynchrony

For synonyms and outdated names see Nomenclature.

1.

For other genetic causes of these phenotypes see Differential Diagnosis.

Diagnosis

Suggestive Findings

OTOF-related deafness should be suspected in individuals with:

  • Congenital auditory neuropathy/synaptopathy without a history of causative environmental factors (e.g., neonatal hyperbilirubinemia and neonatal hypoxia), with or without progression of hearing loss;
  • Temperature-sensitive nonsyndromic auditory neuropathy or synaptopathy.
    Note: OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emission (OAEs) are present. However, in some individuals, OAEs disappear and electrophysiologic testing becomes more consistent with a cochlear defect by several years of age [Chiu et al 2010]. OTOF-related deafness will be identified with physiologic newborn hearing screening if automated ABR is used as part of the screen. If the program uses OAE testing only, the diagnosis may be missed.
  • Family history consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of OTOF-related deafness is established in a proband with suggestive findings and biallelic pathogenic variants in OTOF identified by molecular genetic testing (see Table 1).

Note: Identification of biallelic OTOF variants of uncertain significance (or identification of one known OTOF pathogenic variant and one OTOF variant of uncertain significance) does not establish or rule out a diagnosis of this disorder.

Because the phenotype of OTOF-related deafness may be indistinguishable from many other inherited disorders with deafness, recommended molecular genetic testing approaches include use of a multigene panel or comprehensive genomic testing.

Note: Single-gene testing (sequence analysis of OTOF, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.

  • A hearing loss multigene panel that includes OTOF and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in OTOF-Related Deafness

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
OTOF Sequence analysis 398% 4
Gene-targeted deletion/duplication analysis 5~2% 4, 6
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017], the Deafness Variation Database [Azaiez et al 2018], ClinVar, and Leiden Open Variation Database

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

6.

There have been three reports of a deletion involving OTOF [Zadro et al 2010, Tsai et al 2013, Chang et al 2015]. Two additional deletions were identified at the Molecular Otolaryngology and Renal Research Laboratories [Authors, unpublished observation].

Clinical Characteristics

Clinical Description

The two phenotypes observed in OTOF-related deafness are prelingual nonsyndromic auditory neuropathy spectrum disorder (ANSD) and, less frequently, temperature-sensitive auditory neuropathy spectrum disorder (TS-ANSD), also referred to as auditory synaptopathy, as it is related to a defect in synaptic transmission.

OTOF-related ANSD is characterized by congenital or prelingual, typically severe-to-profound bilateral deafness without inner-ear anomalies on MRI or CT examination of the temporal bones. Otoacoustic emissions (OAEs) are present and auditory brain stem response (ABR) is abnormal at birth. Newborn hearing screening testing only for OAEs will fail to detect this disorder in most individuals. OAEs may decrease or disappear with age in 20%-80% of individuals [Kitao et al 2019].

The hearing loss can range from moderate to profound. (Moderate deafness is defined as hearing loss of 41-55 dB, moderately severe deafness as hearing loss of 56-70 dB, severe deafness as hearing loss of 71-90 dB, and profound deafness as hearing loss of >90 dB.) In some individuals, hearing loss may progress throughout early childhood and adolescence [Chiu et al 2010].

As is typical of auditory neuropathy spectrum disorders, individuals with OTOF-related deafness have poor speech discrimination, and derive significant benefit from cochlear implantation.

TS-ANSD typically presents with normal-to-moderate hearing loss (0-55 dB) at baseline body temperature. An elevation of body temperature (~0.5°C or more) in persons with TS-ANSD triggers significant bilateral hearing loss ranging from severe to profound.

Resolution of hearing loss typically occurs within hours of a return to baseline body temperature. Baseline hearing in children with TS-ANSD has been reported to improve with age in some individuals [Zhang et al 2016b].

Speech discrimination has been described as normal to slightly decreased at baseline with significant worsening during febrile periods. Speech development in these children is dependent on their baseline level of hearing, and benefit has been described from cochlear implantation.

Genotype-Phenotype Correlations

No genotype-phenotype correlations have been identified among the individuals with the OTOF-related ANSD phenotype. Regardless of variant type – truncating versus nontruncating – pathogenic variants in OTOF typically cause severe-to-profound hearing loss (see Figure 1B).

Figure 1:

Figure 1:

Genetic spectrum of OTOF-related hearing loss A. Different types of pathogenic variants have been identified in OTOF, including missense, nonsense, frameshift, splice, inframe indels, and copy number variants (CNV).

However, individuals with TS-ANSD are found to have certain pathogenic variants in OTOF, including p.Arg1939Gln, p.Ile515Thr, p.Gly541Ser, p.Arg1607Trp, and p.Glu1804del (see Table 6).

Nomenclature

Auditory neuropathy can be caused by a number of different defects in the auditory system, including the synaptic region (synaptopathy) or the auditory nerve (neuropathy). Because OTOF-related hearing loss is due to lesions at the presynaptic region of inner hair cells, the terms auditory synaptopathy or auditory neuropathy spectrum disorder are preferred.

Auditory dyssynchrony is a historical term used to describe the mismatch between outer and inner hair cell activity reflected by the difference between ABR and OAE testing.

Prevalence

The prevalence of OTOF pathogenic variants in persons with congenital autosomal recessive nonsyndromic deafness varies depending on ethnic origins. Among individuals with congenital/prelingual autosomal recessive hearing loss, biallelic OTOF pathogenic variants have been found in:

Among individuals with auditory neuropathy spectrum disorder (ANSD), OTOF is a common genetic cause, found in 41%-91% of those tested [Zhang et al 2016a, Kim et al 2018].

The prevalence of temperature-sensitive auditory neuropathy is unknown.

Differential Diagnosis

Congenital (or prelingual) inherited hearing impairment affects approximately one in 1,000 newborns; 30% of these infants have additional anomalies, making the diagnosis of a syndromic form of hearing impairment possible (see Hereditary Hearing Loss and Deafness Overview). In developed countries, approximately half of the remaining children (i.e., the 70% with nonsyndromic hearing impairment) have pathogenic variants in GJB2 [Smith et al 2005, Angeli 2008]. Variants in at least 72 genes (including OTOF) have been implicated in congenital autosomal recessive nonsyndromic deafness.

Differential diagnosis of OTOF-related auditory neuropathy spectrum disorder. Other nonsyndromic hereditary auditory neuropathies include those summarized in Table 2.

Table 2.

Other Nonsyndromic Hereditary Auditory Neuropathy Spectrum Disorders

GenePhenotypeMOIOMIM Entry/Reference
AIFM1 DFNX5XL Zong et al [2015]
DIAPH3 AUNA1AD 609129
PJVK 1DFNB59AR 610220
ROR1 DFNB108AR 617654

Note: OTOF pathogenic variants are extremely unlikely in a child with severe-to-profound hearing loss in only one ear and electrophysiologic responses consistent with auditory neuropathy. Instead, a cochlear defect should be considered; MRI is indicated [Buchman et al 2006].

Differential diagnosis of temperature-sensitive auditory neuropathy spectrum disorder. Other syndromes, such as Muckle-Wells syndrome (cryopyrin-associated periodic syndrome) (OMIM 191900), are associated with progressive deafness and intermittent fevers, but the fever itself does not cause a fluctuating hearing loss [Kuemmerle-Deschner et al 2013].

Management

No clinical practice guidelines for OTOF-related deafness have been published.

Evaluations Following Initial Diagnosis

To establish the extent of involvement in an individual diagnosed with OTOF-related deafness, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with OTOF-Related Deafness

System/ConcernEvaluationComment
Hearing loss /
Deafness
Assessment of auditory acuity (ABR emission testing, pure tone audiometry)
Speech delay By speech therapist / speech pathologist
Speech
discrimination
By audiologistTested when audiometry obtained
Genetic
counseling
By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of OTOF-related deafness to facilitate medical & personal decision making
Family support/
resources
Assess:

ABR = auditory brain stem response; MOI = mode of inheritance

1.

Medical geneticist, certified genetic counselor, or certified advanced genetic nurse

Treatment of Manifestations

Table 4.

Treatment of Manifestations in Individuals with OTOF-Related Deafness

Manifestation/ConcernTreatmentConsiderations/Other
Hearing loss /
Deafness
Hearing aids (HAs)HAs should be fitted as soon as possible after hearing loss is identified. However, based on severity of hearing loss & underlying pathophysiology, HAs are unlikely to be beneficial in many persons.
Cochlear implantation
  • CIs should be considered as soon as possible if hearing aids are not beneficial.
  • Case reports have shown good outcomes w/CIs in persons w/OTOF-related deafness. 1
  • CIs have also been used in TS-ANSD w/beneficial results. 2
Educational programs designed for persons w/hearing impairmentStart as early as possible.
Speech delay Individualized speech therapy

See Hereditary Deafness and Hearing Loss Overview for additional details.

Prevention of Primary Manifestations

For individuals with TS-ANSD:

  • Prevent febrile episodes.
  • Avoid the level of exercise and/or ambient conditions that would cause body temperature to rise.
  • Treat febrile episodes as quickly as possible to return body temperature to normal.
  • Inform individuals and their caregivers that the onset of hearing loss may be the first sign of a pyretic/infectious event requiring treatment [Starr et al 1998].

Surveillance

Table 5.

Recommended Surveillance for Individuals with OTOF-Related Deafness

System/ConcernEvaluationFrequency
Hearing loss / Deafness Audiometry to determine whether hearing loss is progressive or fluctuantEvery 6 mos until age 18 yrs, then annually
Speech recognition Speech discrimination testDone w/audiometry

Agents/Circumstances to Avoid

Avoid the following:

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic sibs of a proband shortly after birth by molecular genetic testing for the pathogenic variants found in the proband so that appropriate early support and management can be provided to the child and family.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Several studies have shown the effectiveness of adeno-associated viral gene therapy to treat OTOF-related hearing loss in animal models [Akil et al 2019, Al-Moyed et al 2019]. Several companies are preparing for clinical trials using this methodology.

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

OTOF-related deafness is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of a child with OTOF-related deafness are obligate heterozygotes (i.e., presumed to be carriers of one OTOF pathogenic variant based on family history).
  • Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an OTOF pathogenic variant and to allow reliable assessment of recurrence probability. (In rare families, only one parent of a proband with an autosomal recessive disorder is heterozygous and the proband is affected as the result of either (1) one pathogenic variant inherited from the heterozygous parent and a second pathogenic variant that occurred de novo in the proband or (2) uniparental isodisomy and consequent homozygosity for the pathogenic variant transmitted by a heterozygous parent [Jónsson et al 2017].)
  • Heterozygotes (carriers) are asymptomatic and do not develop OTOF-related deafness.

Sibs of a proband

  • If both parents are known to be heterozygous for an OTOF pathogenic variant, each sib of the proband has at conception a 25% chance of being deaf, a 50% chance of being a carrier, and a 25% chance of not having a deafness-related variant in OTOF.
  • Heterozygotes (carriers) are asymptomatic and do not develop OTOF-related deafness.

Offspring of a proband. The offspring of an individual with OTOF-related deafness are obligate heterozygotes (carriers of a pathogenic variant in OTOF).

Other family members. For each sib of the proband's parents, the probability of being a carrier of an OTOF pathogenic variant is 50%.

Carrier Detection

Carrier testing for relatives requires prior identification of the OTOF pathogenic variants in the family.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on testing relatives for the purpose of early diagnosis and treatment.

The following points are noteworthy:

  • Communication with individuals who are members of the Deaf community and sign requires the services of a skilled interpreter.
  • Members of the Deaf community may view deafness as a distinguishing characteristic and not as a handicap, impairment, or medical condition requiring a "treatment" or "cure," or to be "prevented."
  • Many deaf people are interested in obtaining information about the cause of their own deafness, including information on medical, educational, and social services, rather than information about prevention, reproduction, or family planning. It is, therefore, important to ascertain and address the questions and concerns of the family/individual.
  • The use of certain terms is preferred: probability or chance vs risk; deaf and hard-of-hearing vs hearing impaired. Terms such as "abnormal" should be avoided.

Family planning

  • The optimal time for determination of genetic status and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of the probability that offspring will be deaf and reproductive options) to young adults who have OTOF-related deafness, are carriers, or may be carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and deafness will improve in the future, consideration should be given to banking DNA of deaf individuals.

Prenatal Testing and Preimplantation Genetic Testing

Once the OTOF pathogenic variants have been identified in a deaf family member, prenatal testing and preimplantation genetic testing for OTOF-related deafness are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Alexander Graham Bell Association for the Deaf and Hard of Hearing
    3417 Volta Place Northwest
    Washington DC 20007
    Phone: 866-337-5220 (toll-free); 202-337-5220; 202-337-5221 (TTY)
    Fax: 202-337-8314
    Email: info@agbell.org
  • American Society for Deaf Children (ASDC)
    800 Florida Avenue Northeast
    Suite 2047
    Washington DC 20002-3695
    Phone: 800-942-2732 (Toll-free Parent Hotline); 866-895-4206 (toll free voice/TTY)
    Fax: 410-795-0965
    Email: info@deafchildren.org; asdc@deafchildren.org
  • BabyHearing.org
    This site, developed with support from the National Institute on Deafness and Other Communication Disorders, provides information about newborn hearing screening and hearing loss.
  • MedlinePlus
  • National Association of the Deaf (NAD)
    8630 Fenton Street
    Suite 820
    Silver Spring MD 20910
    Phone: 301-587-1788; 301-587-1789 (TTY)
    Fax: 301-587-1791
    Email: nad.info@nad.org
  • Newborn Screening in Your State
    Health Resources & Services Administration

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

OTOF-Related Deafness: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for OTOF-Related Deafness (View All in OMIM)

601071DEAFNESS, AUTOSOMAL RECESSIVE 9; DFNB9
603681OTOFERLIN; OTOF

Molecular Pathogenesis

OTOF encodes otoferlin, a member of the FER-1 family of transmembrane proteins characterized by the presence of C2 domains [Yasunaga et al 1999]. Otoferlin contains six C2 domains (C2A-F), a transmembrane domain, and two Fer domains [Roux et al 2006, Lek et al 2010]. In the ear, otoferlin is expressed in cochlear inner hair cells. Otoferlin is a Ca2+ sensor that plays a significant role in the synaptic transmission in inner hair cells by tethering glutamatergic synaptic vesicles to the plasma membrane and triggering their fusion and pool replenishment at ribbon synapses [Strenzke et al 2016, Michalski et al 2017].

Normal hearing relies on a temporally precise and sustained glutamate release at these ribbon synapses. Defects in otoferlin affect this process by compromising exocytosis of synaptic vesicles and their reformation leading to impaired signal transmission to the auditory nerve. Consequently, individuals with biallelic pathogenic variants in OTOF have congenital severe-to-profound hearing loss characterized by normal otoacoustic emission (OAE), indicating normal cochlear function, and abnormal auditory brain stem responses (ABRs), indicating altered transmission of auditory signal from the synapse to the brain and impaired speech discrimination.

To date, more than 220 pathogenic variants have been reported in OTOF [Azaiez et al 2018]. They are distributed all over the gene and affect all domains except C2A domain. Of these variants, 38% were missense, 20% nonsense, 20% frameshift, 17% splice, 3% inframe indel, and 2% copy number variants (CNV) (see Figure 1A). Truncating variants (nonsense, frameshift, splice, and CNV) in OTOF lead to absent or shortened nonfunctional protein. Missense variants impair protein folding, stability, or function. Both types of variants typically result in congenital or prelingual severe-to-profound hearing loss (see Figure 1B).

Certain pathogenic variants in OTOF cause temperature-sensitive auditory neuropathy spectrum disorder (see Table 6). Missense variants cause normal to mild hearing loss when homozygous or compound heterozygous with another missense variant, but when in compound heterozygosity with a truncating variant, the hearing loss is moderate. At normal body temperature, hearing ranges from normal to a moderate loss, while an elevation in body temperature severely worsens hearing loss and speech perception. When temperature decreases, hearing returns to baseline. Studies in mouse models showed that otoferlin is sensitive to heat and this instability is exacerbated by certain pathogenic variants such as Ile515Thr. At increased temperatures, mutated otoferlin undergoes faster degradation and loss from the plasma membrane [Strenzke et al 2016].

Mechanism of disease causation. OTOF-related deafness is caused by loss-of-function pathogenic variants.

OTOF-specific laboratory technical considerations. Variants in OTOF should be annotated on transcript NM_001287489.2, the cochlea-specific transcript.

Table 6.

Notable OTOF Pathogenic Variants

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeComment [Reference]
NM_001287489​.2 c.2485C>Tp.Gln829TerFounder variant in Spanish population [Migliosi et al 2002, Rodríguez-Ballesteros et al 2008]
c.5816G>Ap.Arg1939GlnFounder variant in Japanese population [Matsunaga et al 2012]
c.1544T>Cp.Ile515ThrAssoc w/TS-ANSD [Varga et al 2006]
c.1621G>Ap.Gly541SerAssoc w/TS-ANSD [Matsunaga et al 2012]
c.4819C>Tp.Arg1607TrpAssoc w/TS-ANSD [Wang et al 2010, Zhang et al 2016b]
c.5410_5412delGAGp.Glu1804delAssoc w/TS-ANSD [Marlin et al 2010]

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

TS-ANSD = temperature-sensitive auditory neuropathy spectrum disorder

Chapter Notes

Author Notes

The Hereditary Hearing Loss Homepage (hereditaryhearingloss.org) provides an up-to-date overview of the genetics of hereditary hearing impairment for researchers and clinicians, and lists data and links for all known gene localizations and identifications for monogenic nonsyndromic hearing impairment.

The Deafness Variation Database (DVD) [Azaiez et al 2018] collates, annotates, and classifies all genetic variants related to syndromic and nonsyndromic hearing loss. Data are collated from all major public databases and used to generate an evidence-based single classification for each variant, which is then curated by experts in hereditary hearing loss.

Acknowledgments

The work in this GeneReview was supported in part by grants R01s DC002842, DC012049, and DC017955 (RJHS) and grant 5T32DC000040 (RKT).

Author History

Hela Azaiez, PhD (2021-present)
Jose G Gurrola III, MD; University of Iowa (2007-2015)
Philip M Kelley, PhD; Boys Town National Research Hospital (2007-2015)
A Eliot Shearer, MD, PhD; University of Iowa (2015-2021)
Richard JH Smith, MD (2007-present)
Ryan K Thorpe, MD (2021-present)

Revision History

  • 21 January 2021 (ha) Comprehensive update posted live
  • 30 July 2015 (me) Comprehensive update posted live
  • 14 June 2011 (cd) Revision: link to hearing loss/deafness panel listings in GeneTests Laboratory Directory provided
  • 26 April 2011 (me) Comprehensive update posted live
  • 29 February 2008 (me) Review posted live
  • 15 October 2007 (rjhs) Original submission

References

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