Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.

Autores de IIS La Fe

• Gema García García

  Autor

• 

  José María Millán Salvador

  Autor

Participantes ajenos a IIS La Fe

• Vaché C
• Besnard T
• le Berre P
• Baux D
• Larrieu L
• Abadie C
• Blanchet C
• Bolz HJ
• Hamel C
• Malcolm S
• Claustres M
• Roux AF

Grupos

• 

  Biomedicina Molecular, Celular y Genómica

Abstract

USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified a single pathogenic alteration in one of them and a different mutation in the two affected nieces. As the patients carried a common USH2A haplotype, they likely shared a mutation not found by standard sequencing techniques. Analysis of RNA from nasal cells in one affected individual identified an additional pseudoexon (PE) resulting from a deep intronic mutation. This was confirmed by minigene assay. This is the first example in Usher syndrome (USH) with a mutation causing activation of a PE. The finding of this alteration in eight other individuals of mixed European origin emphasizes the importance of including RNA analysis in a comprehensive diagnostic service. Finally, this mutation, which would not have been found by whole-exome sequencing, could offer, for the first time in USH, the possibility of therapeutic correction by antisense oligonucleotides (AONs).