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

2004 ◽  
Vol 89 (11) ◽  
pp. 5347-5351 ◽  
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.

scholarly journals Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene

2001 ◽  
pp. 697-703 ◽  
Author(s):  
E Sato ◽  
T Nakashima ◽  
Y Miura ◽  
A Furuhashi ◽  
A Nakayama ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Mutation ◽  
Thyroid Volume ◽  
Japanese Patients ◽  
Thyroid Function Tests ◽  
Pendred Syndrome ◽  
Serum Thyroglobulin ◽  
Direct Dna Sequencing ◽  
Vestibular Aqueduct ◽  
Ear Malformations

BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.

Progressive Sensorineural Hearing Loss and a Widened Vestibular Aqueduct in Pendred Syndrome

1998 ◽  
Vol 124 (5) ◽  
pp. 501 ◽  
Author(s):  
Cor W. R. J. Cremers ◽  
Cuny Bolder ◽  
Ronald J. C. Admiraal ◽  
Lorraine A. Everett ◽  
Frank B. M. Joosten ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Pendred Syndrome ◽  
Vestibular Aqueduct

scholarly journals Fluctuating Sensorineural Hearing Loss

2019 ◽  
Vol 24 (3) ◽  
pp. 109-116 ◽  
Author(s):  
Hui Liu ◽  
Kunpeng Zhou ◽  
Xuemei Zhang ◽  
Kevin A. Peng
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Current Treatment ◽  
Sensorineural Hearing ◽  
Initial Presentation ◽  
Vestibular Aqueduct ◽  
Long Term Follow Up ◽  
Inner Ear Disease ◽  
Fluctuating Hearing Loss

Background: Several otologic conditions can present with fluctuating sensorineural hearing loss, including Ménière’s disease, autoimmune inner ear disease, and enlarged vestibular aqueduct. Although these 3 etiologies vary greatly, distinguishing between these conditions at initial presentation can be challenging. Furthermore, initial treatment of these conditions is often similar. In this review, we discuss historical and current perspectives on diagnosis and treatment of these conditions. Summary: A literature search was performed regarding fluctuating hearing loss, and current treatment of these etiologies of fluctuating hearing loss was summarized. Immediate measures at the onset of acute hearing loss include corticosteroid therapy, while preventative and chronic therapies, which can limit disease severity and frequency, vary based on the specific condition treated. Key Messages: Fluctuating hearing loss can represent a range of pathologies, but the precise etiology may not be clear at initial presentation. Timely treatment and long-term follow-up, along with appropriate diagnostics, are necessary to optimize long-term hearing.

scholarly journals Study on the relationship between the pathogenic mutations of SLC26A4 and CT phenotypes of inner ear in patient with sensorineural hearing loss

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Lihua Wu ◽  
Yunliang Liu ◽  
Jianman Wu ◽  
Sheng Chen ◽  
Shupin Tang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Ct Scan ◽  
Inner Ear ◽  
Gene Mutations ◽  
Pathogenic Mutation ◽  
Vestibular Aqueduct ◽  
Slc26a4 Gene ◽  
Pathogenic Mutations ◽  
Inner Ear Malformation ◽  
Single Allele

Abstract To investigate the possible association of pathogenic mutations of SLC26A4 and computerized tomography (CT) phenotypes of inner ear, and explore the feasibility of using the method of gene sequence analysis. A total of 155 patients with bilateral hearing loss carrying SLC26A4 gene mutations were further subjected to high-resolution temporal bone CT and thyroid B ultrasound tests. The potential relationship between the pathogenic mutations of gene and the CT phenotypes were analyzed. As a result, 65 patients (41.9%, 65/155) carried SLC26A4 gene mutations, and 27 cases were detected with pathogenic mutations of SLC26A4 where IVS7-2A>G (55.6%, 15/27) was the most common pathogenic mutation. Amongst them, 19 patients carrying bi-allelic SLC26A4 mutations were all confirmed to have inner ear malformation by CT scan including four cases of enlarged vestibular aqueduct (EVA) and 15 cases of Mondini dysplasia (MD). However, there was only one in eight cases of single allele pathogenic mutation who was confirmed to have EVA by CT scan. Further, only one patient with EVA was confirmed to be slightly higher of total T3 than normal by thyroid ultrasound scan and thyroid hormone assays. These findings suggested that CT detection and SLC26A4 gene detection are efficient methods to diagnose EVA, which can complement each other. Also, the bi-allelic pathogenic mutations of SLC26A4 are more likely to induce inner ear malformation than single allele pathogenic mutation.

The Natural History of Hearing Loss in Pendred Syndrome and Non-Syndromic Enlarged Vestibular Aqueduct

2019 ◽  
Vol 40 (3) ◽  
pp. e178-e185 ◽  
Author(s):  
Kristianna Mey ◽  
Michael Bille ◽  
Stig Hebbelstrup Rye Rasmussen ◽  
Lisbeth Tranebjærg ◽  
Per Cayé-Thomasen
Keyword(s):  
Hearing Loss ◽  
Natural History ◽  
Pendred Syndrome ◽  
Enlarged Vestibular Aqueduct ◽  
Vestibular Aqueduct ◽  
History Of

scholarly journals Different Rates of the SLC26A4-Related Hearing Loss in Two Indigenous Peoples of Southern Siberia (Russia)

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2378
Author(s):  
Valeriia Yu. Danilchenko ◽  
Marina V. Zytsar ◽  
Ekaterina A. Maslova ◽  
Marita S. Bady-Khoo ◽  
Nikolay A. Barashkov ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genetic Diagnosis ◽  
Unknown Etiology ◽  
Pendred Syndrome ◽  
Genetic Causes ◽  
Asian Populations ◽  
Slc26a4 Gene ◽  
Medical Genetic Services ◽  
First Time ◽  
Local Healthcare

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.

scholarly journals Enlarged vestibular aqueduct and Mondini Malformation: audiological, clinical, radiologic and genetic features

2020 ◽  
Author(s):  
F. Forli ◽  
F. Lazzerini ◽  
G. Auletta ◽  
L. Bruschini ◽  
S. Berrettini
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Late Onset ◽  
Pure Tone Audiometry ◽  
Enlarged Vestibular Aqueduct ◽  
Vestibular Aqueduct ◽  
Genetic Features ◽  
Ear Malformations ◽  
Caucasian Patients ◽  
Genetic Assessment

Abstract Purpose When referring to enlarged vestibular aqueduct (EVA) we should differentiate between nonsyndromic enlarged vestibular aqueduct (NSEVA) and Pendred Syndrome (PDS), a disease continuum associated with pathogenic sequence variants of Pendrin’s Gene (SLC26A4) in about half of the cases. The study was aimed to analyse the clinical and audiological features of a monocentric cohort of Caucasian patients with NSEVA/PDS, their genetic assessment and morphological inner ear features. Methods We retrospectively reviewed the audiologic, genetic and anamnestic data of 66 patients with NSEVA/PDS followed by our audiology service. Results SLC26A4 mutations was significantly correlated with the presence of PDS rather than NSEVA (p < 0.019), with the expression of inner ear malformations (p < 0.001) and with different severity of hearing loss (p = 0.001). Furthermore, patients with PDS showed significantly worse pure tone audiometry (PTA) than patients with NSEVA (p = 0.001). Anatomically normal ears presented significantly better PTA than ears associated with Mondini Malformation or isolated EVA (p < 0.001), but no statistically significative differences have been observed in PTA between patients with Mondini Malformation and isolated EVA. Conclusion NSEVA/PDS must be investigated in all the congenital hearing loss, but also in progressive, late onset, stepwise forms. Even mixed or fluctuating hearing loss may constitute a sign of a NSEVA/PDS pathology. Our findings can confirm the important role of SLC26A4 mutations in determining the phenotype of isolated EVA/PDS, both for the type/degree of the malformation, the hearing impairment and the association with thyroid dysfunction.

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