The Mitochondrial tRNAHis G12192A Mutation May Modulate the Clinical Expression of Deafness-Associated tRNAThr G15927A Mutation in a Chinese Pedigree

2019 ◽  
Vol 19 (2) ◽  
pp. 136-146 ◽  
Author(s):  
Yu Ding ◽  
Yao-Shu Teng ◽  
Guang-Chao Zhuo ◽  
Bo-Hou Xia ◽  
Jian-Hang Leng
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Ros Generation ◽  
Trna Genes ◽  
Variable Degree ◽  
Clinical Expression ◽  
Atp Production ◽  
Molecular Features ◽  
Potential Association ◽  
Syndromic Hearing Loss

Background: Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with both syndromic and non-syndromic hearing impairment. However, the pathophysiology underlying mt-tRNA mutations in clinical expression of hearing loss remains poorly understood. Objective: The aim of this study was to explore the potential association between mttRNA mutations and hearing loss. Methods and Results: We reported here the molecular features of a pedigree with maternally transmitted non-syndromic hearing loss. Among 12 matrilineal relatives, five of them suffered variable degree of hearing impairment, but none of them had any medical history of using aminoglycosides antibiotics (AmAn). Genetic screening of the complete mitochondrial genomes from the matrilineal relatives identified the coexistence of mt-tRNAHis G12192A and mt-tRNAThr G15927A mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup B5b1b. Interestingly, the G12192A mutation occurred 2-bp from the 3’ end of the TψC loop of mt-tRNAHis, which was evolutionarily conserved from various species. In addition, the well-known G15927A mutation, which disrupted the highly conserved C-G base-pairing at the anticodon stem of mt-tRNAThr, may lead to the failure in mt-tRNA metabolism. : Furthermore, a significant decreased in ATP production and an increased ROS generation were observed in polymononuclear leukocytes (PMNs) which were isolated from the deaf patients carrying these mt-tRNA mutations, suggested that the G12192A and G15927A mutations may cause mitochondrial dysfunction that was responsible for deafness. However, the absence of any functional mutations/variants in GJB2, GJB3, GJB6 and TRMU genes suggested that the nuclear genes may not play important roles in the clinical expression of non-syndromic hearing loss in this family. Conclusion: Our data indicated that mt-tRNAHis G12192A mutation may increase the penetrance and expressivity of deafness-associated m-tRNAThr G15927A mutation in this family.

Hearing impairment caused by mutations in two different genes responsible for nonsyndromic and syndromic hearing loss within a single family

2017 ◽  
Vol 59 (1) ◽  
pp. 67-72
Author(s):  
Katarzyna Niepokój ◽  
Agnieszka M. Rygiel ◽  
Piotr Jurczak ◽  
Aleksandra A Kujko ◽  
Dominika Śniegórska ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Single Family ◽  
Syndromic Hearing Loss

scholarly journals A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1711
Author(s):  
Ting-Ting Yen ◽  
I-Chieh Chen ◽  
Men-Wei Hua ◽  
Chia-Yi Wei ◽  
Kai-Hsiang Shih ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Late Onset ◽  
Clinical Manifestations ◽  
Pure Tone Audiometry ◽  
The Elderly ◽  
High Frequency Hearing Loss ◽  
Increased Risk ◽  
Syndromic Hearing Loss ◽  
Precision Medicine Initiative

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

scholarly journals When transcripts matter: delineating between non-syndromic hearing loss DFNB32 and hearing impairment infertile male syndrome (HIIMS)

2020 ◽  
Vol 65 (7) ◽  
pp. 609-617
Author(s):  
Marzieh Mohseni ◽  
Mojdeh Akbari ◽  
Kevin T. Booth ◽  
Mojgan Babanejad ◽  
Hela Azaiez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Infertile Male ◽  
Syndromic Hearing Loss

scholarly journals Study on Hearing Status of Elderly Patients attending a Specialized ENT Hospital (SAHIC)

2016 ◽  
Vol 21 (2) ◽  
pp. 80-84
Author(s):  
Mohammad Wakilur Rahman ◽  
Ali Imam Ahasan ◽  
Timir Kumar Debnath ◽  
Abul Naser Md Jamil ◽  
Raju Barua ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Elderly Patients ◽  
Hearing Impairment ◽  
Past History ◽  
Cross Sectional Study ◽  
Hearing Level ◽  
Variable Degree ◽  
Cross Sectional ◽  
Socioeconomic Condition ◽  
Age Related

Background: Age related hearing loss is a natural process in elderly population all over the world.Objectives: To determine the hearing level of elderly patients in relation to age, sex, socioeconomic condition and to determine the pattern and extent of hearing loss in old age.Method: This cross sectional study was carried out at out patient department of Specialized ENT Hospital of SAHIC, Mohakhali, Dhaka, from October 2012 to March 2013. 200 patients were included with age > 50 years and who have no past history of drug therapy. Data were collected by detailed history, clinical examination and audiometric findings and result were expressed in table form.Result: 57% patients were found with normal hearing and 43% had variable degree of hearing impairment. Highest number of hearing impairment was found in 9th decade. Most of hearing loss were found to be bilateral and sensorineural in type.Conclusion: A good number of elderly people in our country is suffering from some degree of hearing loss, which are mostly sensorineural in type. The prevalence and severity of hearing loss increases with increasing age.Bangladesh J Otorhinolaryngol; October 2015; 21(2): 80-84

Occurrence of del( GIB6 -D13S1830) mutation in italian non-syndromic hearing loss patients carrying a single GJB2 mutated allele

2004 ◽  
Vol 124 (0) ◽  
pp. 29-34 ◽  
Author(s):  
F. Gualandi ◽  
A. Ravani ◽  
A. Berto ◽  
S. Burdo ◽  
P. Trevisi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Syndromic Hearing Loss

Feasibility of smartphone-based hearing-aid apps for patients with mild hearing loss: an exploratory pilot study (Preprint)

2020 ◽  
Author(s):  
Willy Nguyen ◽  
Miseung Koo ◽  
Seung Ha Oh ◽  
Jun Ho Lee ◽  
Moo Kyun Park
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Hearing Aids ◽  
Clinical Performance ◽  
Hearing Aid ◽  
National Standards ◽  
Hearing In Noise ◽  
Mild Hearing Loss ◽  
Consumer Devices ◽  
Selection Of

BACKGROUND Underuse of hearing aids is caused by several factors, including the stigma associated with hearing disability, affordability, and lack of awareness of rising hearing impairment associated with the growing population. Thus, there is a significant opportunity for the development of direct-to-consumer devices. For the past few years, smartphone-based hearing-aid apps have become more numerous and diverse, but few studies have investigated them. OBJECTIVE This study aimed to elucidate the electroacoustic characteristics and potential user benefits of a selection of currently available hearing-aid apps. METHODS We investigated the apps based on hearing-aid control standards (American National Standards Institute) using measurement procedures from previous studies. We categorized the apps and excluded those we considered inefficient. We investigated a selection of user-friendly, low-end apps, EarMachine and Sound Amplifier, with warble-tone audiometry, word recognition testing in unaided and aided conditions, and hearing-in-noise test in quiet and noise-front conditions in a group of users with mild hearing impairment (n = 7) as a pilot for a future long-term investigation. Results from the apps were compared with those of a conventional hearing aid. RESULTS Five of 14 apps were considered unusable based on low scores in several metrics, while the others varied across the range of electroacoustic measurements. The apps that we considered “high end” that provided lower processing latencies and audiogram-based fitting algorithms were superior overall. The clinical performance of the listeners tended to be better when using hearing aid, while the low end hearing-aid apps had limited benefits on the users. CONCLUSIONS Some apps showed the potential to benefit users with limited cases of minimal or mild hearing loss if the inconvenience of relatively poor electroacoustic performance did not outweigh the benefits of amplification.

scholarly journals Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

2021 ◽  
Vol 22 (12) ◽  
pp. 6497
Author(s):  
Anna Ghilardi ◽  
Alberto Diana ◽  
Renato Bacchetta ◽  
Nadia Santo ◽  
Miriam Ascagni ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Muscle Fibers ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Developmental Defects ◽  
Inner Ear Development ◽  
Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

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