Novel FERMT3 and PTPRQ Mutations Associated with Leukocyte Adhesion Deficiency-III and Sensorineural Hearing Loss

2021 ◽  
Author(s):  
Gabriela de Toledo Passos Candelaria ◽  
Alexandre de A. Antunes ◽  
Antonio C. Pastorino ◽  
Mayra de B. Dorna ◽  
Evelin A. Zanardo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Leukocyte Adhesion ◽  
Tyrosine Phosphatase ◽  
Sensorineural Hearing ◽  
Leukocyte Adhesion Deficiency ◽  
Brazilian Patient ◽  
And Function ◽  
Genotype Correlation

AbstractLeukocyte adhesion deficiency-III (LAD-III) is a rare genetic disease caused by defective integrin activation in hematopoietic cells due to mutations in the FERMT3 gene. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q and is essential for the normal maturation and function of hair bundle in the cochlea. Homozygous PTPRQ mutations impair the stereocilia in hair cells which lead to nonsyndromic sensorineural hearing loss (SNHL) with vestibular dysfunction. Here, we report two novel pathogenic homozygous mutations found in two genes, FERMT3 and PTPRQ, in a Brazilian patient with LAD-III and SNHL, which may develop our understanding of the phenotype–genotype correlation and prognosis of patients with these rare diseases.

scholarly journals Autosomal Recessive Congenital Sensorineural Hearing Loss due to a Novel Compound Heterozygous PTPRQ Mutation in a Chinese Family

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xia Wu ◽  
Shan Wang ◽  
Sen Chen ◽  
Ying-ying Wen ◽  
Bo Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Tyrosine Phosphatase ◽  
Sensorineural Hearing ◽  
Paternal Allele ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Gene Encoding ◽  
Sequencing Method ◽  
And Function

PTPRQ gene, encoding protein tyrosine phosphatase receptor Q, is essential for the normal maturation and function of hair bundle in the cochlea. Its mutations can cause the defects of stereocilia in hair cell, which lead to nonsyndromic sensorineural hearing loss. Using next-generation sequencing and Sanger sequencing method, we identified a novel compound heterozygous missense mutation, c.4472C>T p.T1491M (maternal allele) and c.1973T>C p.V658A (paternal allele), in PTPRQ gene. The two mutations are the first reported to be the cause of recessively inherited sensorineural hearing loss. Hearing loss levels and progression involved by PTPRQ mutations among the existing cases seem to be varied, and the relationship between genotypes and phenotypes is unclear. Our data here further prove the important role of PTPRQ in auditory function and provide more information for the further mechanism research of PTPRQ-related hearing loss.

scholarly journals Noise-induced and age-related hearing loss:  new perspectives and potential therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 927 ◽  
Author(s):  
M Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Cell Loss ◽  
Sensorineural Hearing ◽  
Hair Cell Loss ◽  
Age Related ◽  
Age Related Hearing Loss

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

scholarly journals Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

2021 ◽  
Vol 8 ◽  
Author(s):  
Melanie Holmgren ◽  
Lavinia Sheets
Keyword(s):  
Cell Death ◽  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Lateral Line ◽  
Hair Cells ◽  
High Energy ◽  
Sensorineural Hearing ◽  
Mitochondrial Activity ◽  
Ototoxic Drugs

Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug–induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans.

scholarly journals Sensorineural Hearing Loss Due to Exposure of Noisy Trains on Populations Around Turirejo Train Railroad Cross

2020 ◽  
Vol 12 (1) ◽  
pp. 59
Author(s):  
Diana Kusuma Wardhani ◽  
Jojok Mukono Mukono
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Noise Intensity ◽  
Noise Exposure ◽  
Sound Level ◽  
Sensorineural Hearing ◽  
High Noise ◽  
Railroad Tracks ◽  
The Government

Introduction: As one of the preferred modes of land transportation, the frequency of train services was very high. One of the negative impacts arising from train activity was noise. The high noise intensity of the train causes hearing loss. Method: This study aims to analyze the differences in the incidence of hearing loss in 2 groups of residents in Turirejo Lawang Malang. This research used the observational method and the data were analyzed descriptive qualitative. A total of 20 people were selected as respondents by purposive sampling. Noise intensity was measured by Sound Level Meter and audiometric measurements were examined at SIMA Malang Laboratory. Result and Discussion: The prevalence of sensorineural hearing loss was more common in residents whose homes at 3-7 m away from the railroad tracks. In addition, residents who lived at least 15 years at a distance of 3-7 m also experienced more hearing loss. One cause of hearing loss is due to exposure to high noise and for a long time and will damage the hair cells in the cochlea, causing hearing loss. If noise exposure continues and for a long period of time damage to hair cells will be permanent and cannot return to normal. Conclusion: There needs to be a policy from the government in determining the minimum limit of the distance of the house to the railroad tracks. In addition, it is necessary to install a barrier near people’s homes to reduce noise.

scholarly journals Autophagy Regulates the Survival of Hair Cells and Spiral Ganglion Neurons in Cases of Noise, Ototoxic Drug, and Age-Induced Sensorineural Hearing Loss

2021 ◽  
Vol 15 ◽  
Author(s):  
Lingna Guo ◽  
Wei Cao ◽  
Yuguang Niu ◽  
Shuangba He ◽  
Renjie Chai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Spiral Ganglion ◽  
Sensorineural Hearing ◽  
Spiral Ganglion Neurons ◽  
Core Components ◽  
Spontaneous Regeneration ◽  
Ganglion Neurons

Inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) are the core components of the auditory system. However, they are vulnerable to genetic defects, noise exposure, ototoxic drugs and aging, and loss or damage of HCs and SGNs results in permanent hearing loss due to their limited capacity for spontaneous regeneration in mammals. Many efforts have been made to combat hearing loss including cochlear implants, HC regeneration, gene therapy, and antioxidant drugs. Here we review the role of autophagy in sensorineural hearing loss and the potential targets related to autophagy for the treatment of hearing loss.

scholarly journals Correlation between Carotid–Cochlear and Sensorineural Hearing Loss: A Cross-Sectional Study

2018 ◽  
Vol 01 (02) ◽  
pp. 089-093
Author(s):  
Raghul Sekar ◽  
Arun Alexander ◽  
Nagarajan Krishnan
Keyword(s):  
Hearing Loss ◽  
Carotid Artery ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Fluid Pressure ◽  
Sensorineural Deafness ◽  
Normal Subjects ◽  
Sensorineural Hearing ◽  
P Value ◽  
Strong Negative Correlation

Abstract Background Sensorineural hearing loss is a condition with several etiologies and varies with the age of the individual. Carotid–cochlear interval is the minimum distance between basal turn of cochlea and the genu of petrous part of internal carotid artery. It is believed that constant pulsations from carotid can cause fluid pressure changes within the cochlea leading to damage to hair cells causing hearing loss. Objective To study the correlation between carotid–cochlear interval and degree of hearing loss at different frequencies in patients with sensorineural deafness and compare this interval with normal subjects. Methods Seventy cases with sensorineural hearing loss between 18 and 60 years undergoing HRCT temporal bone were grouped together and 70 cases with normal hearing undergoing CT nose and paranasal sinuses were grouped together. Carotid–cochlear interval measured in both the groups was correlated with the degree and frequency of hearing loss and compared with normal subjects. Results The mean carotid–cochlear interval in sensorineural hearing loss and in normal subjects was found to be 1.30 + 0.68 (SD) mm and 1.83 + 0.74 (SD) mm, respectively with p < 0.001. The coefficient of correlation between carotid–cochlear interval and pure tone average in patients with sensorineural deafness was r = −0.740 with p-value < 0.001. Conclusion Carotid–cochlear interval is significantly low in patients with sensorineural hearing loss and bears a strong negative correlation with the degree of hearing loss at mid- and high-frequency ranges. Thus we hypothesize that pulsations from carotid artery cause damage to hair cells in the organ of Corti producing audiological symptoms such as hearing loss.

Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms

2020 ◽  
pp. jmedgenet-2020-106892
Author(s):  
Xue Gao ◽  
Sha-Sha Huang ◽  
Shi-Wei Qiu ◽  
Yu Su ◽  
Wei-Qian Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Noonan Syndrome ◽  
Sensorineural Hearing ◽  
Supporting Cells ◽  
Pathogenic Variants ◽  
Underlying Mechanisms ◽  
Ganglion Neurons ◽  
Multiple Lentigines

BackgroundGermline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which share common skin and facial symptoms, cardiac anomalies and retardation of growth. Hearing loss is considered an infrequent feature in patients with NSML/NS. However, in our cohort, we identified a group of patients with PTPN11 pathogenic variants that were primarily manifested in congenital sensorineural hearing loss (SNHL). This study evaluated the incidence of PTPN11-related NSML or NS in patients with congenital SNHL and explored the expression of PTPN11 and the underlying mechanisms in the auditory system.MethodsA total of 1502 patients with congenital SNHL were enrolled. Detailed phenotype-genotype correlations were analysed in patients with PTPN11 variants. Immunolabelling of Ptpn11 was performed in P35 mice. Zebrafish with Ptpn11 knockdown/mutant overexpression were constructed to further explore mechanism underlying the phenotypes.ResultsTen NSML/NS probands were diagnosed via the identification of pathogenic variants of PTPN11, which accounted for ~0.67% of the congenital SNHL cases. In mice cochlea, Shp2, which is encoded by Ptpn11, is distributed in the spiral ganglion neurons, hair cells and supporting cells of the inner ear. In zebrafish, knockdown of ptpn11a and overexpression of mutant PTPN11 were associated with a significant decrease in hair cells and supporting cells. We concluded that congenital SNHL could be a major symptom in PTPN11-associated NSML or NS. Other features may be mild, especially in children.ConclusionScreening for PTPN11 in patients with congenital hearing loss and variant-based diagnoses are recommended.

scholarly journals N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Xue Bai ◽  
Sen Chen ◽  
Kai Xu ◽  
Yuan Jin ◽  
Xun Niu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Control Group ◽  
Hearing Recovery ◽  
Potential Strategy ◽  
Intratympanic Dexamethasone ◽  
Pure Tone Threshold

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant–antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.

Sign in / Sign up

Export Citation Format

Share Document