scholarly journals Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

2022 ◽  
Author(s):  
Shin-ichi Usami ◽  
Yuichi Isaka ◽  
Maiko Miyagawa ◽  
Shin-ya Nishio
Keyword(s):  
Hearing Loss ◽  
Late Onset ◽  
Usher Syndrome ◽  
Asian Population ◽  
Profound Hearing Loss ◽  
Mutational Spectrum ◽  
Age Related ◽  
Syndromic Hearing Loss ◽  
Age Related Hearing Loss ◽  
Usher Syndrome Type

AbstractVariants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause a broad range of phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high-frequency-involved progressive hearing loss. In this study, based on the genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the East Asian population in general, as well as frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combinations) and phenotype (association with retinal pigmentosa, onset age) are shown to be well correlated and are thought to be related to the residual function defined by the CDH23 variants.

scholarly journals Variants in CDH23 Cause Broad Spectrum of Hearing Loss: From Non-Syndromic to Syndromic Hearing Loss as Well as From Congenital to Age-Related Hearing Loss

2021 ◽  
Author(s):  
Shin-ichi Usami ◽  
Yuichi Isaka ◽  
Maiko Miyagawa ◽  
Shin-ya Nishio
Keyword(s):  
Hearing Loss ◽  
Late Onset ◽  
Usher Syndrome ◽  
Asian Population ◽  
Profound Hearing Loss ◽  
Mutational Spectrum ◽  
Age Related ◽  
Syndromic Hearing Loss ◽  
Age Related Hearing Loss ◽  
Usher Syndrome Type

Abstract Variants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause broad phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high frequency-involved progressive hearing loss. In this study, using genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the east Asian population in general, and the frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combination) and phenotype (association of retinal pigmentosa, onset age) are shown to be well correlated, and are thought to be related to the residual function defined by the CDH23 variants.

scholarly journals Usher syndrome Type I in an adult Nepalese male: a rare case report

2018 ◽  
Vol 9 (2) ◽  
pp. 203-205
Author(s):  
Sabin Sahu ◽  
Sanjay Kumar Singh
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Genetic Disorder ◽  
Usher Syndrome ◽  
Type I ◽  
Syndrome Type ◽  
Profound Hearing Loss ◽  
Rare Case Report ◽  
Different Populations ◽  
Usher Syndrome Type

Usher syndrome, also known as retinitis pigmentosa-dysacusis syndrome, is an extremely rare genetic disorder, characterized by retinitis pigmentosa (RP) and congenital sensorineural hearing loss. It has been estimated to account for 3-6% of the congenitally deaf population, upto 8-33% of individuals with RP and half of all cases with combined deafness and blindness (Vernon M,1969; Boughman JA et al,1983). The prevalence of Usher syndrome have been reported to range from 3.5 to 6.2 per 100,000 in different populations (Vernon M,1969; Boughman JA et al,1983; Yan D et al, 2010).We report a case of Usher syndrome type I in an adult Nepalese male with typical congenital profound hearing loss, and night blindness secondary to retinitis pigmentosa.

scholarly journals Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

2021 ◽  
Vol 22 (5) ◽  
pp. 2510
Author(s):  
John Hoon Rim ◽  
Jae Young Choi ◽  
Jinsei Jung ◽  
Heon Yung Gee
Keyword(s):  
Hearing Loss ◽  
Late Onset ◽  
Ion Homeostasis ◽  
Physiological Role ◽  
Voltage Gated ◽  
Age Related ◽  
Gated Channel ◽  
Pros And Cons ◽  
Age Related Hearing Loss

Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing to genetic mutations is responsible for nonsyndromic hearing loss, a typically late-onset, initially high-frequency loss progressing over time. In addition, variants of KCNQ4 have also been associated with noise-induced hearing loss and age-related hearing loss. Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss. In this review, we updated the current concept of the physiological role of KCNQ4 in the inner ear and the pathologic mechanism underlying the role of KCNQ4 variants with regard to hearing loss. Finally, we focused on currently developed KCNQ4 activators and their pros and cons, paving the way for the future development of specific KCNQ4 activators as a remedy for hearing loss.

Usher syndrome

2021 ◽  
pp. 495-497
Author(s):  
Shanees. E
Keyword(s):  
Hearing Loss ◽  
Early Diagnosis ◽  
Vision Loss ◽  
Treatment Success ◽  
Usher Syndrome ◽  
Autosomal Recessive Disorder ◽  
Type I ◽  
Profound Hearing Loss ◽  
Balance Problems ◽  
Usher Syndrome Type

Usher syndrome is a condition that affects both hearing and vision; sometimes it also affects balance. The major symptoms of Usher syndrome are deafness or hearing loss and an eye disease called retinitis pigmentosa (RP). Most children with Usher syndrome are born with moderate to profound hearing loss, depending on the type. Less commonly, hearing loss from Usher syndrome appears during adolescence or later.1 Usher syndrome affects approximately 4 to 17 per 100,000 people,2,3 and accounts for about 50 percent of all hereditary deaf- blindness cases.4 . Usher syndrome is inherited as an autosomal recessive disorder. Usher syndrome is caused by mutations in specific genes. So far, Usher syndrome has been associated with mutations in at least ten genes. There are three types of Usher syndrome, type I, type II and type III 1. Diagnosis of Usher syndrome involves pertinent questions regarding the person’s medical history and testing of hearing, balance, and vision. Early diagnosis is important, as it improves treatment success. Genetic testing may help in diagnosing Usher syndrome. Presently, there is no cure for Usher syndrome. Treatment involves managing hearing, vision, and balance problems. Early diagnosis helps tailor educational programs that consider the severity of hearing and vision loss and a child’s age and ability.1 Usher Syndrome Awareness Day is observed in the third Saturday of September. Usher Syndrome Awareness Day seeks to bring attention and raise awareness of the most common genetic cause of combined deafness and blindness.5

scholarly journals THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis

2019 ◽  
Author(s):  
Luping Zhang ◽  
Yu Gao ◽  
Ru Zhang ◽  
Feifei Sun ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Cell Apoptosis ◽  
Late Onset ◽  
Nonsyndromic Hearing Loss ◽  
Progressive Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Shed Light

AbstractApoptosis of cochlear hair cells is a key step towards age-related hearing loss. Although numerous genes have been implicated in the genetic causes of late-onset, progressive hearing loss, few show direct links to the proapoptotic process. By genome-wide linkage analysis and whole exome sequencing, we identified a heterozygous p.L183V variant in THOC1 as the probable cause of the late-onset, progressive, non-syndromic hearing loss in a large dominant family. Thoc1, a member of the conserved multisubunit THO/TREX ribonucleoprotein complex, is highly expressed in mouse and zebrafish hair cells. The Thoc1 mutant zebrafish generated by gRNA-Cas9 system lacks the C-startle response, indicative of the hearing dysfunction. Both Thoc1 mutant and knockdown zebrafish have greatly reduced hair cell numbers, while the latter can be rescued by embryonic microinjection of human wild-type THOC1 mRNA but to significantly lesser degree by the p.L183V mutant mRNA. The Thoc1 deficiency resulted in marked apoptosis in zebrafish hair cells. Consistently, transcriptome sequencing of the mutants showed significantly increased gene expression in the p53-associated signaling pathway. Depletion of p53 or applying the p53 inhibitor Pifithrin-α significantly rescued the hair cell loss in the Thoc1 knockdown zebrafish. Our results suggested that THOC1 deficiency lead to late-onset, progressive hearing loss through p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.Significance StatementFor the first time, we found that THOC1 deficiency leads to late-onset nonsyndromic hearing loss. Furthermore, we revealed the hypomorphic THOC1 induced p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.

Risk Factors of Age-related Hearing Loss, Adults over 65 Years in Korea: Including the Effect of the War Participation

2016 ◽  
Vol 17 (2) ◽  
pp. 68-73
Author(s):  
Dong-Wook Kim ◽  
Tae-Young Lee ◽  
Da-Hye Choi ◽  
Taek-Yeong Kim ◽  
Hyun-Chul Moon
Keyword(s):  
Risk Factors ◽  
Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2853
Author(s):  
Judit Szepesy ◽  
Viktória Humli ◽  
János Farkas ◽  
Ildikó Miklya ◽  
Júlia Tímár ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Dose Range ◽  
Auditory Brainstem ◽  
High Frequency Hearing Loss ◽  
Age Related ◽  
Hearing Function ◽  
Brainstem Response ◽  
Aging Societies ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15–45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

scholarly journals Reduced resting state functional connectivity with increasing age-related hearing loss and McGurk susceptibility

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alina Schulte ◽  
Christiane M. Thiel ◽  
Anja Gieseler ◽  
Maike Tahden ◽  
Hans Colonius ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Functional Connectivity ◽  
Resting State ◽  
Mcgurk Effect ◽  
Functional Coupling ◽  
Resting State Functional Connectivity ◽  
Visual Integration ◽  
Age Related ◽  
Hearing Thresholds ◽  
Age Related Hearing Loss

Abstract Age-related hearing loss has been related to a compensatory increase in audio-visual integration and neural reorganization including alterations in functional resting state connectivity. How these two changes are linked in elderly listeners is unclear. The current study explored modulatory effects of hearing thresholds and audio-visual integration on resting state functional connectivity. We analysed a large set of resting state data of 65 elderly participants with a widely varying degree of untreated hearing loss. Audio-visual integration, as gauged with the McGurk effect, increased with progressing hearing thresholds. On the neural level, McGurk illusions were negatively related to functional coupling between motor and auditory regions. Similarly, connectivity of the dorsal attention network to sensorimotor and primary motor cortices was reduced with increasing hearing loss. The same effect was obtained for connectivity between the salience network and visual cortex. Our findings suggest that with progressing untreated age-related hearing loss, functional coupling at rest declines, affecting connectivity of brain networks and areas associated with attentional, visual, sensorimotor and motor processes. Especially connectivity reductions between auditory and motor areas were related to stronger audio-visual integration found with increasing hearing loss.

Sign in / Sign up

Export Citation Format

Share Document