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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8703989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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