Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss

Noben-Trauth, Konrad; Zheng, Qing Yin; Johnson, Kenneth R.

doi:10.1038/ng1226

Cited by 426 publications

(459 citation statements)

References 16 publications

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“…On the other hand, genetic complementation tests have shown allelism between ahl1 and mdfw, and both are found to add to the severity of HL caused by mutation of the Atp2b2 gene [41]. It was subsequently shown that the Ahl1 gene might also be allelic to Cdh23 v [42]. Thus, Cdh23 may be an important gene that may be involved not only in certain forms of congenital deafness but also in ARHL, and has the potential to genetically interact with other deafness genes to affect hearing.…”

Section: Heritability Allelism and Genetic Modifiers Of Presbycusismentioning

confidence: 99%

“…Thus, Cdh23 may be an important gene that may be involved not only in certain forms of congenital deafness but also in ARHL, and has the potential to genetically interact with other deafness genes to affect hearing. One synonymous single-nucleotide polymorphism (SNP) in Cdh23 (753G>A) was indeed found associated with AHL and the deafness modifier mdfw [42]. The Cdh23 753A variant causes in-frame skipping of exon 7.…”

Section: Heritability Allelism and Genetic Modifiers Of Presbycusismentioning

confidence: 99%

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Ageing and hearing loss

Yan

2007

The Journal of Pathology

278

178

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Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved.

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Section: Heritability Allelism and Genetic Modifiers Of Presbycusismentioning

confidence: 99%

Section: Heritability Allelism and Genetic Modifiers Of Presbycusismentioning

confidence: 99%

Ageing and hearing loss

Yan

2007

The Journal of Pathology

278

178

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“…Cdh23 ϩ/ϩ mice show a moderate increase in hearing thresholds with increasing age, which we attribute to the presence of the agerelated hearing loss Cdh23 753A allele in C57BL6/J mice. 8 However, Cdh23 V2360E/ϩ heterozygous mice exhibit a statistically significant (P ϭ 0.0018) increase in hearing thresholds at the age of 24 weeks when compared with Cdh23 ϩ/ϩ wild-type littermates using two-way analysis of variance ( Figure 5). There was no sign of vestibular dysfunction in jera because behavioral test results, including movement, circling, head tossing/tilting, star-gazing behavior, and righting response (curl trunk test), were normal in all three genotypes.…”

Section: Loss Of Auditory Function In Cdh23 V2360e/v2360e Micementioning

confidence: 97%

“…[2][3][4][5][6][7] A synonymous single-nucleotide polymorphism, Cdh23 753A , is linked to age-related hearing loss in mice. 8 Null mutations in mouse Cdh23 lead to the waltzer phenotype, characterized by hearing loss and vestibular dysfunction. 9 -13 Two N-ethyl-N-nitrosourea (ENU)-generated mouse strains, salsa and erlong, carry a recessive Cdh23 missense mutation.…”

mentioning

confidence: 99%

An ENU-Induced Mutation of Cdh23 Causes Congenital Hearing Loss, but No Vestibular Dysfunction, in Mice

Manji

Miller

Williams

et al. 2011

The American Journal of Pathology

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Mutations in the human cadherin 23 (CDH23) gene cause deafness, neurosensory, autosomal recessive 12 (DFNB12) nonsyndromic hearing loss or Usher syndrome, type 1D (characterized by hearing impairment, vestibular dysfunction, and visual impairment). Reported waltzer mouse strains each harbor a Cdh23-null mutation and present with hearing loss and vestibular dysfunction. Two additional Cdh23 mouse mutants, salsa and erlong, each carry a homozygous Cdh23 missense mutation and have progressive hearing loss. We report the identification of a novel mouse strain, jera, with inherited hearing loss caused by an N-ethyl-N-nitrosourea-induced c.7079T>A mutation in the Cdh23 gene. The mutation generates a missense change, p.V2360E, in Cdh23. Affected mice have profound sensorineural deafness, with no vestibular dysfunction. The p.V2360E mutation is semidominant because heterozygous mice have milder and more progressive hearing loss in advanced age. The mutation affects a highly conserved Ca 2؉ -binding motif in extracellular domain 22, thought to be important for Cdh23 structure and dimerization. Molecular modeling suggests that the Cdh23 V2360E/V2360E mutation alters the structural conformation of the protein and affects Ca 2؉ -binding properties. Similar to salsa mice, but in contrast to waltzer mice, hair bundle development is normal in jera and hearing loss appears to be due to the loss of tip links. Thus, jera is a novel mouse model for DFNB12. (Am J Pathol 2011, 179:903-914;

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“…A number of genes and their protein products have been reported to be involved in both age-and noise-related hearing loss [10][11][12][13][14][15]. Cadherin and protocadherin mutations were linked to digenic inheritance of deafness and have specific functional roles in noise-induced hearing loss [13][14][16][17].…”

Section: Introductionmentioning

confidence: 99%

Preliminary studies on differential expression of auditory functional genes in the brain after repeated blast exposures

Valiyaveettil

Alamneh²,

Miller³

et al. 2012

JRRD

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Abstract-The mechanisms of central auditory processing involved in auditory/vestibular injuries and subsequent tinnitus and hearing loss in Active Duty servicemembers exposed to blast are not currently known. We analyzed the expression of hearingrelated genes in different regions of the brain 6 h after repeated blast exposures in mice. Preliminary data showed that the expression of the deafness-related genes otoferlin and otoancorin was significantly changed in the hippocampus after blast exposures. Differential expression of cadherin and protocadherin genes, which are involved in hearing impairment, was observed in the hippocampus, cerebellum, frontal cortex, and midbrain after repeated blasts. A series of calcium-signaling genes that are known to be involved in auditory signal processing were also found to be significantly altered after repeated blast exposures. The hippocampus and midbrain showed significant increase in the gene expression of hearing loss-related antioxidant enzymes. Histopathology of the auditory cortex showed more significant injury in the inner layer compared to the outer layer. In summary, mice exposed to repeated blasts showed injury to the auditory cortex and significant alterations in multiple genes in the brain known to be involved in age-or noise-induced hearing impairment.

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Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss

Cited by 426 publications

References 16 publications

Ageing and hearing loss

Ageing and hearing loss

An ENU-Induced Mutation of Cdh23 Causes Congenital Hearing Loss, but No Vestibular Dysfunction, in Mice

Preliminary studies on differential expression of auditory functional genes in the brain after repeated blast exposures

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