The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2021

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

Luke Mansard
David Baux
Christel Vaché
Catherine Blanchet
  • Function : Author
Isabelle Meunier
  • Function : Author
Marjolaine Willems
Valérie Faugère
  • Function : Author
Corinne Baudoin
  • Function : Author
Melody Moclyn
  • Function : Author
Julie Bianchi
  • Function : Author
Helene Dollfus
  • Function : Author
Brigitte Gilbert-Dussardier
  • Function : Author
Delphine Dupin-Deguine
  • Function : Author
Dominique Bonneau
  • Function : Author
Isabelle Drumare
  • Function : Author
Sylvie Odent
  • Function : Author
Xavier Zanlonghi
  • Function : Author
Mireille Claustres
  • Function : Author
Vasiliki Kalatzis
Anne-Françoise Roux

Abstract

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.
Fichier principal
Vignette du fichier
2021 Mansard et al., The study.pdf (46.56 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03503346 , version 1 (28-12-2021)

Identifiers

Cite

Luke Mansard, David Baux, Christel Vaché, Catherine Blanchet, Isabelle Meunier, et al.. The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A. International Journal of Molecular Sciences, 2021, 22 (24), pp.13294. ⟨10.3390/ijms222413294⟩. ⟨hal-03503346⟩
22 View
9 Download

Altmetric

Share

Gmail Facebook X LinkedIn More