A mutational analysis of the SLC26A4 gene in Spanish hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and DFNB4 hearing loss.

Hereditary hearing loss (HL) is known to be highly locus/allelic heterogeneous, and the prevalence of different HL forms significantly varies among populations worldwide. Investigation of region-specific landscapes of hereditary HL is important for local healthcare and medical genetic services. Mutations in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4) and Pendred syndrome are common genetic causes of hereditary HL, at least in some Asian populations. We present for the first time the results of a thorough analysis of the SLC26A4 gene by Sanger sequencing in the large cohorts of patients with HL of unknown etiology belonging to two neighboring indigenous Turkic-speaking Siberian peoples (Tuvinians and Altaians). A definite genetic diagnosis based on the presence of biallelic SLC26A4 mutations was established for 28.2% (62/220) of all enrolled Tuvinian patients vs. 4.3% (4/93) of Altaian patients. The rate of the SLC26A4-related HL in Tuvinian patients appeared to be one of the highest among populations worldwide. The SLC26A4 mutational spectrum was characterized by the presence of Asian-specific mutations c.919-2A>G and c.2027T>A (p.Leu676Gln), predominantly found in Tuvinian patients, and c.2168A>G (p.His723Arg), which was only detected in Altaian patients. In addition, a novel pathogenic variant c.1545T>G (p.Phe515Leu) was found with high frequency in Tuvinian patients. Overall, based on the findings of this study and our previous research, we were able to uncover the genetic causes of HL in 50.5% of Tuvinian patients and 34.5% of Altaian patients.

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Clinical heterogeneity of the SLC26A4 gene in UAE patients with hearing loss and bioinformatics investigation of DFNB4/Pendred syndrome missense mutations

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2020.110467 ◽

2021 ◽

Vol 140 ◽

pp. 110467

Author(s):

Jihen Chouchen ◽

Mona Mahfood ◽

Maryam Alobathani ◽

Walaa Kamal Eldin Mohamed ◽

Abdelaziz Tlili

Keyword(s):

Hearing Loss ◽

Missense Mutations ◽

Clinical Heterogeneity ◽

Pendred Syndrome ◽

Slc26a4 Gene

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Pendred Syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000800015 ◽

2008 ◽

Vol 52 (8) ◽

pp. 1296-1303 ◽

Cited By ~ 7

Author(s):

Adriana Lofrano-Porto ◽

Gustavo B. Barra ◽

Paula P. Nascimento ◽

Patrícia G. G. Costa ◽

Érica C. Garcia ◽

...

Keyword(s):

Hearing Loss ◽

Phenotypic Variability ◽

Sensorineural Deafness ◽

Molecular Characteristics ◽

Homozygous Mutation ◽

Thyroid Function Tests ◽

Pendred Syndrome ◽

Slc26a4 Gene ◽

Organification Defect ◽

Temporal Bones

Pendred Syndrome (PS) is an autossomal recessive disorder characterized by sensorineural deafness, goiter and iodide organification defect. The hearing loss is associated with inner ear abnormalities, ranging from an isolated enlarged vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to be associated with PS. We describe the clinical and molecular characteristics of a large consanguineous family harboring a mutation in the SLC26A4 gene. The proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular goiter and hypothyroidism since puberty. Five other siblings were deaf: one brother had a similar phenotype, three siblings also had goiters but normal thyroid function tests, and one brother had only a subtle thyroid enlargement. Other 4 siblings had no thyroid or hearing disorder. Parents were first degree cousins and had normal hearing. The mother was healthy, except for subclinical hypothyroidism; the father was deceased. A perchlorate test in the proband showed a discharge of 21% of the incorporated iodide 2h after the administration of 1g of KClO4. Audiological examinations showed profound hearing loss in all deaf subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the mother and control. The coding region of the PDS gene (exons 2-21), including exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair (T) deletion at position 1197 of exon 10 was detected in homozygous state in the 6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this mutation, which has been described by Everett et al. The 1197delT mutation is predicted to result in a frameshift and a truncated protein. The existence of PS phenocopies and intrafamilial phenotypic variability are well documented. The definite diagnosis requires molecular analysis. Our study illustrates the value and challenges of mutational analysis in selected patients with PS.

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Intrafamilial Variability of the Deafness and Goiter Phenotype in Pendred Syndrome Caused by a T416P Mutation in the SLC26A4 Gene

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1013 ◽

2004 ◽

Vol 89 (11) ◽

pp. 5347-5351 ◽

Cited By ~ 21

Author(s):

Ulrike Napiontek ◽

Guntram Borck ◽

Wiebke Müller-Forell ◽

Nicole Pfarr ◽

Andrea Bohnert ◽

...

Keyword(s):

Hearing Loss ◽

Distinct Type ◽

Pendred Syndrome ◽

Phenotypic Differences ◽

Vestibular Aqueduct ◽

Slc26a4 Gene ◽

Sequence Variations ◽

Ear Malformations ◽

Long Term Follow Up ◽

Bilateral Sensorineural Hearing Loss

Abstract Pendred syndrome (PS) is the most common cause of syndromic deafness, accounting for more than 5% of all autosomal-recessive hearing loss cases. It is characterized by bilateral sensorineural hearing loss and by goiter with or without hypothyroidism. Mutations in the SLC26A4 gene cause both classical PS and deafness associated with an enlarged vestibular aqueduct without goiter. To investigate a possible genotype-phenotype correlation in PS, we performed a detailed clinical and genetic study in three adult German sibs with typical PS caused by a common homozygous SLC26A4 mutation, T416P. An audiological long-term follow-up of 23 yr showed that the mutation T416P is associated with a distinct type of hearing loss in each of the three sibs: moderate-to-profound progressive deafness, profound nonprogressive deafness, and a milder but more rapidly progressing form. We show that these phenotypic differences are not caused by either different degrees of inner ear malformations or sequence variations in the GJB2/connexin 26 gene. Because the thyroid phenotype was also highly variable within the family, with thyroid sizes ranging from normal to large goiters requiring thyroidectomy, this study leads to the conclusion that other environmental and/or genetic factors have an impact on the PS phenotype.

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Mutational analysis of the SLC26A4 gene in Chinese sporadic nonsyndromic hearing-impaired children

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2012.06.027 ◽

2012 ◽

Vol 76 (10) ◽

pp. 1474-1480 ◽

Cited By ~ 12

Author(s):

Xiangyang Hu ◽

Fenghe Liang ◽

Min Zhao ◽

Angela Gong ◽

Emily R. Berry ◽

...

Keyword(s):

Mutational Analysis ◽

Hearing Impaired ◽

Slc26a4 Gene ◽

Impaired Children ◽

Hearing Impaired Children

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Teacher Identification of Elementary School Children with Hearing Loss

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.0901.24 ◽

1978 ◽

Vol 9 (1) ◽

pp. 24-28 ◽

Cited By ~ 1

Author(s):

Richard H. Nodar

Keyword(s):

Elementary School ◽

Hearing Loss ◽

School Children ◽

Elementary School Children ◽

Total Sample ◽

Hearing Impaired ◽

Teacher Interviews ◽

Teacher Screening ◽

Children With Hearing Loss ◽

Hearing Problems

The teachers of 2231 elementary school children were asked to identify those with known or suspected hearing problems. Following screening, the data were compared. Teachers identified 5% of the children as hearing-impaired, while screening identified only 3%. There was agreement between the two procedures on 1%. Subsequent to the teacher interviews, rescreening and tympanometry were conducted. These procedures indicated that teacher screening and tympanometry were in agreement on 2% of the total sample or 50% of the hearing-loss group. It was concluded that teachers could supplement audiometry, particularly when otoscopy and typanometry are not available.

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The impact of hearing loss

ORL ro ◽

10.26416/orl.33.4.2016.170 ◽

2016 ◽

Vol 4 (1) ◽

pp. 64-65

Author(s):

Mădălina Georgescu ◽

Violeta Necula ◽

Sebastian Cozma

Keyword(s):

Hearing Loss ◽

Health Services ◽

Hard Of Hearing ◽

Hearing Impaired ◽

Public Health Issue ◽

Health Politics ◽

Universal Newborn Hearing Screening ◽

Newborn Hearing ◽

Impaired Person ◽

The Impact

Hearing loss represents a frequently met sensorial handicap, which has a major and complex impact not only on the hearing-impaired person, but also on his family and society. The large number of hard-of-hearing persons justifies the acknowledgement of hearing loss as a public health issue, which oblige to appropriate health politics, to offer each hearing-impaired person health services like those in Europe. These can be obtained through: appropriate legislation for mandatory universal newborn hearing screening; national program for follow-up of hearing-impaired children up to school age; national register of hard-of-hearing persons; smooth access to rehabilitation methods; appropriate number of audiologists, trained for health services at European standards, trained through public programs of education in the field of audiology.

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Speech Perception and Sound-Quality Rating with an Adaptive Nonlinear Frequency Compression Algorithm in Mandarin-Speaking Hearing Aid Users

Journal of the American Academy of Audiology ◽

10.1055/s-0040-1709450 ◽

2020 ◽

Vol 31 (08) ◽

pp. 590-598

Author(s):

Li Xu ◽

Solveig C. Voss ◽

Jing Yang ◽

Xianhui Wang ◽

Qian Lu ◽

...

Keyword(s):

Hearing Loss ◽

Hearing Aids ◽

Detection Threshold ◽

Sound Quality ◽

Hearing Impaired ◽

Nonlinear Frequency ◽

Frequency Compression ◽

Speech Reception ◽

Quality Ratings ◽

Phoneme Detection

Abstract Background Mandarin Chinese has a rich repertoire of high-frequency speech sounds. This may pose a remarkable challenge to hearing-impaired listeners who speak Mandarin Chinese because of their high-frequency sloping hearing loss. An adaptive nonlinear frequency compression (adaptive NLFC) algorithm has been implemented in contemporary hearing aids to alleviate the problem. Purpose The present study examined the performance of speech perception and sound-quality rating in Mandarin-speaking hearing-impaired listeners using hearing aids fitted with adaptive NLFC (i.e., SoundRecover2 or SR2) at different parameter settings. Research Design Hearing-impaired listeners' phoneme detection thresholds, speech reception thresholds, and sound-quality ratings were collected with various SR2 settings. Study Sample The participants included 15 Mandarin-speaking adults aged 32 to 84 years old who had symmetric sloping severe-to-profound sensorineural hearing loss. Intervention The participants were fitted bilaterally with Phonak Naida V90-SP hearing aids. Data Collection and Analysis The outcome measures included phoneme detection threshold using the Mandarin Phonak Phoneme Perception test, speech reception threshold using the Mandarin hearing in noise test (M-HINT), and sound-quality ratings on human speech in quiet and noise, bird chirps, and music in quiet. For each test, five experimental settings were applied and compared: SR2-off, SR2-weak, SR2-default, SR2-strong 1, and SR2-strong 2. Results The results showed that listeners performed significantly better with SR2-strong 1 and SR2-strong 2 settings than with SR2-off or SR2-weak settings for speech reception threshold and phoneme detection threshold. However, no significant improvement was observed in sound-quality ratings among different settings. Conclusions These preliminary findings suggested that the adaptive NLFC algorithm provides perceptual benefit to Mandarin-speaking people with severe-to-profound hearing loss.

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Perception of Auditory Distance in Normal-Hearing and Moderate-to-Profound Hearing-Impaired Listeners

Trends in Hearing ◽

10.1177/2331216519887615 ◽

2019 ◽

Vol 23 ◽

pp. 233121651988761 ◽

Cited By ~ 3

Author(s):

Gilles Courtois ◽

Vincent Grimaldi ◽

Hervé Lissek ◽

Philippe Estoppey ◽

Eleftheria Georganti

Keyword(s):

Hearing Loss ◽

Hearing Aids ◽

Normal Hearing ◽

Hearing Impaired ◽

Spatial Cues ◽

Linear Amplification ◽

Profound Hearing Loss ◽

Wireless Microphone ◽

Auditory Distance ◽

Non Linear

The auditory system allows the estimation of the distance to sound-emitting objects using multiple spatial cues. In virtual acoustics over headphones, a prerequisite to render auditory distance impression is sound externalization, which denotes the perception of synthesized stimuli outside of the head. Prior studies have found that listeners with mild-to-moderate hearing loss are able to perceive auditory distance and are sensitive to externalization. However, this ability may be degraded by certain factors, such as non-linear amplification in hearing aids or the use of a remote wireless microphone. In this study, 10 normal-hearing and 20 moderate-to-profound hearing-impaired listeners were instructed to estimate the distance of stimuli processed with different methods yielding various perceived auditory distances in the vicinity of the listeners. Two different configurations of non-linear amplification were implemented, and a novel feature aiming to restore a sense of distance in wireless microphone systems was tested. The results showed that the hearing-impaired listeners, even those with a profound hearing loss, were able to discriminate nearby and far sounds that were equalized in level. Their perception of auditory distance was however more contracted than in normal-hearing listeners. Non-linear amplification was found to distort the original spatial cues, but no adverse effect on the ratings of auditory distance was evident. Finally, it was shown that the novel feature was successful in allowing the hearing-impaired participants to perceive externalized sounds with wireless microphone systems.

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