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Pendred Syndrome, or Not Pendred Syndrome? That Is the Question

Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study a...

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Autores principales: Tesolin, Paola, Fiorino, Sofia, Lenarduzzi, Stefania, Rubinato, Elisa, Cattaruzzi, Elisabetta, Ammar, Lydie, Castro, Veronica, Orzan, Eva, Granata, Claudio, Dell’Orco, Daniele, Morgan, Anna, Girotto, Giorgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535891/
https://www.ncbi.nlm.nih.gov/pubmed/34680964
http://dx.doi.org/10.3390/genes12101569
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author Tesolin, Paola
Fiorino, Sofia
Lenarduzzi, Stefania
Rubinato, Elisa
Cattaruzzi, Elisabetta
Ammar, Lydie
Castro, Veronica
Orzan, Eva
Granata, Claudio
Dell’Orco, Daniele
Morgan, Anna
Girotto, Giorgia
author_facet Tesolin, Paola
Fiorino, Sofia
Lenarduzzi, Stefania
Rubinato, Elisa
Cattaruzzi, Elisabetta
Ammar, Lydie
Castro, Veronica
Orzan, Eva
Granata, Claudio
Dell’Orco, Daniele
Morgan, Anna
Girotto, Giorgia
author_sort Tesolin, Paola
collection PubMed
description Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study aims to define the molecular diagnosis for a cohort of 24 suspected-PDS patients characterized by a deep radiological and audiological evaluation. Whole-Exome Sequencing (WES), the analysis of twelve variants upstream of SLC26A4, constituting the “CEVA haplotype” and Multiplex Ligation Probe Amplification (MLPA) searching for deletions/duplications in SLC26A4 gene have been carried out. In five patients (20.8%) homozygous/compound heterozygous SLC26A4 mutations, or pathogenic mutation in trans with the CEVA haplotype have been identified, while five subjects (20.8%) resulted heterozygous for a single variant. In silico protein modeling supported the pathogenicity of the detected variants, suggesting an effect on the protein stabilization/function. Interestingly, we identified a genotype-phenotype correlation among those patients carrying SLC26A4 mutations, whose audiograms presented a characteristic slope at the medium and high frequencies, providing new insights into PDS. Finally, an interesting homozygous variant in MYO5C has been identified in one patient negative to SLC26A4 gene, suggesting the identification of a new HL candidate gene.
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spelling pubmed-85358912021-10-23 Pendred Syndrome, or Not Pendred Syndrome? That Is the Question Tesolin, Paola Fiorino, Sofia Lenarduzzi, Stefania Rubinato, Elisa Cattaruzzi, Elisabetta Ammar, Lydie Castro, Veronica Orzan, Eva Granata, Claudio Dell’Orco, Daniele Morgan, Anna Girotto, Giorgia Genes (Basel) Article Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study aims to define the molecular diagnosis for a cohort of 24 suspected-PDS patients characterized by a deep radiological and audiological evaluation. Whole-Exome Sequencing (WES), the analysis of twelve variants upstream of SLC26A4, constituting the “CEVA haplotype” and Multiplex Ligation Probe Amplification (MLPA) searching for deletions/duplications in SLC26A4 gene have been carried out. In five patients (20.8%) homozygous/compound heterozygous SLC26A4 mutations, or pathogenic mutation in trans with the CEVA haplotype have been identified, while five subjects (20.8%) resulted heterozygous for a single variant. In silico protein modeling supported the pathogenicity of the detected variants, suggesting an effect on the protein stabilization/function. Interestingly, we identified a genotype-phenotype correlation among those patients carrying SLC26A4 mutations, whose audiograms presented a characteristic slope at the medium and high frequencies, providing new insights into PDS. Finally, an interesting homozygous variant in MYO5C has been identified in one patient negative to SLC26A4 gene, suggesting the identification of a new HL candidate gene. MDPI 2021-10-01 /pmc/articles/PMC8535891/ /pubmed/34680964 http://dx.doi.org/10.3390/genes12101569 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tesolin, Paola
Fiorino, Sofia
Lenarduzzi, Stefania
Rubinato, Elisa
Cattaruzzi, Elisabetta
Ammar, Lydie
Castro, Veronica
Orzan, Eva
Granata, Claudio
Dell’Orco, Daniele
Morgan, Anna
Girotto, Giorgia
Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title_full Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title_fullStr Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title_full_unstemmed Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title_short Pendred Syndrome, or Not Pendred Syndrome? That Is the Question
title_sort pendred syndrome, or not pendred syndrome? that is the question
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535891/
https://www.ncbi.nlm.nih.gov/pubmed/34680964
http://dx.doi.org/10.3390/genes12101569
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