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Autosomal dominant auditory neuropathy 1(NSDAN; AUNA1)

MedGen UID:
322984
•Concept ID:
C1836743
•
Disease or Syndrome
Synonym: AUDITORY NEUROPATHY, NONSYNDROMIC DOMINANT
 
Gene (location): DIAPH3 (13q21.2)
 
Monarch Initiative: MONDO:0012196
OMIM®: 609129

Definition

Auditory neuropathy is a type of hearing loss defined by the preservation of cochlear outer hair cell function and abnormal or absent auditory brainstem responses. Auditory neuropathy may accompany peripheral neuropathy in a variety of dominant syndromes such as Charcot-Marie-Tooth disease (Satya-Murti et al., 1979) and has been observed in Friedreich ataxia (Satya-Murti et al., 1980). Auditory neuropathy unassociated with peripheral neuropathy most commonly occurs as a sporadic or recessive trait; see, for example, 601071. Genetic Heterogeneity of Autosomal Dominant Auditory Neuropathy See also AUNA2 (620384), caused by mutation in the ATP11A gene (605868) on chromosome 13q34, and AUNA3 (619832), caused by mutation in the TMEM43 gene (612048) on chromosome 3p25. [from OMIM]

Clinical features

From HPO
Sensorineural hearing loss disorder
MedGen UID:
9164
•Concept ID:
C0018784
•
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
See: Feature record | Search on this feature
Absence of acoustic reflex
MedGen UID:
322049
•Concept ID:
C1832834
•
Finding
Absence of the acoustic reflex, an involuntary contraction of the stapedius muscle that occurs in response to high-intensity sound stimuli.
See: Feature record | Search on this feature
Abnormal speech discrimination
MedGen UID:
322986
•Concept ID:
C1836752
•
Finding
A type of hearing impairment prominently characterized by a difficulty in understanding speech, rather than an inability to hear speech. Poor speech discrimination is a very common symptom of high frequency hearing loss.
See: Feature record | Search on this feature
Abnormal auditory evoked potentials
MedGen UID:
141758
•Concept ID:
C0522216
•
Finding
An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.
See: Feature record | Search on this feature
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Recent clinical studies

Etiology

Pure monosomy and pure trisomy of 13q21.2-31.1 consequent to a familial insertional translocation: exclusion of PCDH9 as the responsible gene for autosomal dominant auditory neuropathy (AUNA1).
Grati FR, Lesperance MM, De Toffol S, Chinetti S, Selicorni A, Emery S, Grimi B, Dulcetti F, Malvestiti B, Taylor J, Milani S, Ruggeri AM, Maggi F, Simoni G
Am J Med Genet A 2009 May;149A(5):906-13. doi: 10.1002/ajmg.a.32754. PMID: 19353688
Human cytomegalovirus (HCMV) and hearing impairment: infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49 -- both involved in dominantly inherited, sensorineural, hearing impairment.
Nystad M, Fagerheim T, Brox V, Fortunato EA, Nilssen Ø
Mutat Res 2008 Jan 1;637(1-2):56-65. Epub 2007 Jul 25 doi: 10.1016/j.mrfmmm.2007.07.009. PMID: 17765268Free PMC Article
Anticipation in a unique family with Charcot-Marie-Tooth syndrome and deafness: delineation of the clinical features and review of the literature.
Kovach MJ, Campbell KC, Herman K, Waggoner B, Gelber D, Hughes LF, Kimonis VE
Am J Med Genet 2002 Apr 1;108(4):295-303. doi: 10.1002/ajmg.10223. PMID: 11920834

Diagnosis

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.
Jang MW, Oh DY, Yi E, Liu X, Ling J, Kim N, Sharma K, Kim TY, Lee S, Kim AR, Kim MY, Kim MA, Lee M, Han JH, Han JJ, Park HR, Kim BJ, Lee SY, Woo DH, Oh J, Oh SJ, Du T, Koo JW, Oh SH, Shin HW, Seong MW, Lee KY, Kim UK, Shin JB, Sang S, Cai X, Mei L, He C, Blanton SH, Chen ZY, Chen H, Liu X, Nourbakhsh A, Huang Z, Kang KW, Park WY, Feng Y, Lee CJ, Choi BY
Proc Natl Acad Sci U S A 2021 Jun 1;118(22) doi: 10.1073/pnas.2019681118. PMID: 34050020Free PMC Article
A novel variant in diaphanous homolog 1 (DIAPH1) as the cause of auditory neuropathy in a Chinese family.
Wu K, Wang H, Guan J, Lan L, Zhao C, Zhang M, Wang D, Wang Q
Int J Pediatr Otorhinolaryngol 2020 Jun;133:109947. Epub 2020 Feb 13 doi: 10.1016/j.ijporl.2020.109947. PMID: 32087478
Molecular study of patients with auditory neuropathy.
Carvalho GM, Ramos PZ, Castilho AM, Guimarães AC, Sartorato EL
Mol Med Rep 2016 Jul;14(1):481-90. Epub 2016 May 9 doi: 10.3892/mmr.2016.5226. PMID: 27177047
Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.
Mutai H, Suzuki N, Shimizu A, Torii C, Namba K, Morimoto N, Kudoh J, Kaga K, Kosaki K, Matsunaga T
Orphanet J Rare Dis 2013 Oct 28;8:172. doi: 10.1186/1750-1172-8-172. PMID: 24164807Free PMC Article
Anticipation in a unique family with Charcot-Marie-Tooth syndrome and deafness: delineation of the clinical features and review of the literature.
Kovach MJ, Campbell KC, Herman K, Waggoner B, Gelber D, Hughes LF, Kimonis VE
Am J Med Genet 2002 Apr 1;108(4):295-303. doi: 10.1002/ajmg.10223. PMID: 11920834

Prognosis

Molecular Impairment Mechanisms of Novel OPA1 Mutations Predicted by Molecular Modeling in Patients With Autosomal Dominant Optic Atrophy and Auditory Neuropathy Spectrum Disorder.
Namba K, Mutai H, Takiguchi Y, Yagi H, Okuyama T, Oba S, Yamagishi R, Kaneko H, Shintani T, Kaga K, Matsunaga T
Otol Neurotol 2016 Apr;37(4):394-402. doi: 10.1097/MAO.0000000000000978. PMID: 26905822
Diaphanous homolog 3 (Diap3) overexpression causes progressive hearing loss and inner hair cell defects in a transgenic mouse model of human deafness.
Schoen CJ, Burmeister M, Lesperance MM
PLoS One 2013;8(2):e56520. Epub 2013 Feb 18 doi: 10.1371/journal.pone.0056520. PMID: 23441200Free PMC Article
Anticipation in a unique family with Charcot-Marie-Tooth syndrome and deafness: delineation of the clinical features and review of the literature.
Kovach MJ, Campbell KC, Herman K, Waggoner B, Gelber D, Hughes LF, Kimonis VE
Am J Med Genet 2002 Apr 1;108(4):295-303. doi: 10.1002/ajmg.10223. PMID: 11920834

Clinical prediction guides

Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss.
Gilels FA, Wang J, Bullen A, White PM, Kiernan AE
Cell Death Dis 2022 Nov 18;13(11):971. doi: 10.1038/s41419-022-05380-w. PMID: 36400760Free PMC Article
A novel variant in diaphanous homolog 1 (DIAPH1) as the cause of auditory neuropathy in a Chinese family.
Wu K, Wang H, Guan J, Lan L, Zhao C, Zhang M, Wang D, Wang Q
Int J Pediatr Otorhinolaryngol 2020 Jun;133:109947. Epub 2020 Feb 13 doi: 10.1016/j.ijporl.2020.109947. PMID: 32087478
Molecular Impairment Mechanisms of Novel OPA1 Mutations Predicted by Molecular Modeling in Patients With Autosomal Dominant Optic Atrophy and Auditory Neuropathy Spectrum Disorder.
Namba K, Mutai H, Takiguchi Y, Yagi H, Okuyama T, Oba S, Yamagishi R, Kaneko H, Shintani T, Kaga K, Matsunaga T
Otol Neurotol 2016 Apr;37(4):394-402. doi: 10.1097/MAO.0000000000000978. PMID: 26905822
Diaphanous homolog 3 (Diap3) overexpression causes progressive hearing loss and inner hair cell defects in a transgenic mouse model of human deafness.
Schoen CJ, Burmeister M, Lesperance MM
PLoS One 2013;8(2):e56520. Epub 2013 Feb 18 doi: 10.1371/journal.pone.0056520. PMID: 23441200Free PMC Article
Anticipation in a unique family with Charcot-Marie-Tooth syndrome and deafness: delineation of the clinical features and review of the literature.
Kovach MJ, Campbell KC, Herman K, Waggoner B, Gelber D, Hughes LF, Kimonis VE
Am J Med Genet 2002 Apr 1;108(4):295-303. doi: 10.1002/ajmg.10223. PMID: 11920834

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