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The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the mo...

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Autores principales: Mansard, Luke, Baux, David, Vaché, Christel, Blanchet, Catherine, Meunier, Isabelle, Willems, Marjolaine, Faugère, Valérie, Baudoin, Corinne, Moclyn, Melody, Bianchi, Julie, Dollfus, Helene, Gilbert-Dussardier, Brigitte, Dupin-Deguine, Delphine, Bonneau, Dominique, Drumare, Isabelle, Odent, Sylvie, Zanlonghi, Xavier, Claustres, Mireille, Koenig, Michel, Kalatzis, Vasiliki, Roux, Anne-Françoise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703989/
https://www.ncbi.nlm.nih.gov/pubmed/34948090
http://dx.doi.org/10.3390/ijms222413294
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author Mansard, Luke
Baux, David
Vaché, Christel
Blanchet, Catherine
Meunier, Isabelle
Willems, Marjolaine
Faugère, Valérie
Baudoin, Corinne
Moclyn, Melody
Bianchi, Julie
Dollfus, Helene
Gilbert-Dussardier, Brigitte
Dupin-Deguine, Delphine
Bonneau, Dominique
Drumare, Isabelle
Odent, Sylvie
Zanlonghi, Xavier
Claustres, Mireille
Koenig, Michel
Kalatzis, Vasiliki
Roux, Anne-Françoise
author_facet Mansard, Luke
Baux, David
Vaché, Christel
Blanchet, Catherine
Meunier, Isabelle
Willems, Marjolaine
Faugère, Valérie
Baudoin, Corinne
Moclyn, Melody
Bianchi, Julie
Dollfus, Helene
Gilbert-Dussardier, Brigitte
Dupin-Deguine, Delphine
Bonneau, Dominique
Drumare, Isabelle
Odent, Sylvie
Zanlonghi, Xavier
Claustres, Mireille
Koenig, Michel
Kalatzis, Vasiliki
Roux, Anne-Françoise
author_sort Mansard, Luke
collection PubMed
description Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed.
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spelling pubmed-87039892021-12-25 The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A Mansard, Luke Baux, David Vaché, Christel Blanchet, Catherine Meunier, Isabelle Willems, Marjolaine Faugère, Valérie Baudoin, Corinne Moclyn, Melody Bianchi, Julie Dollfus, Helene Gilbert-Dussardier, Brigitte Dupin-Deguine, Delphine Bonneau, Dominique Drumare, Isabelle Odent, Sylvie Zanlonghi, Xavier Claustres, Mireille Koenig, Michel Kalatzis, Vasiliki Roux, Anne-Françoise Int J Mol Sci Article Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed. MDPI 2021-12-10 /pmc/articles/PMC8703989/ /pubmed/34948090 http://dx.doi.org/10.3390/ijms222413294 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
Mansard, Luke
Baux, David
Vaché, Christel
Blanchet, Catherine
Meunier, Isabelle
Willems, Marjolaine
Faugère, Valérie
Baudoin, Corinne
Moclyn, Melody
Bianchi, Julie
Dollfus, Helene
Gilbert-Dussardier, Brigitte
Dupin-Deguine, Delphine
Bonneau, Dominique
Drumare, Isabelle
Odent, Sylvie
Zanlonghi, Xavier
Claustres, Mireille
Koenig, Michel
Kalatzis, Vasiliki
Roux, Anne-Françoise
The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title_full The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title_fullStr The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title_full_unstemmed The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title_short The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A
title_sort study of a 231 french patient cohort significantly extends the mutational spectrum of the two major usher genes myo7a and ush2a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703989/
https://www.ncbi.nlm.nih.gov/pubmed/34948090
http://dx.doi.org/10.3390/ijms222413294
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