Description of Two Siblings with Apparently Severe CEP290 Mutations and Unusually Mild Retinal Disease Unrelated to Basal Exon Skipping or Nonsense-Associated Altered Splicing

Details

Serval ID
serval:BIB_8F62D9954191
Type
A part of a book
Publication sub-type
Chapter: chapter ou part
Collection
Publications
Institution
Title
Description of Two Siblings with Apparently Severe CEP290 Mutations and Unusually Mild Retinal Disease Unrelated to Basal Exon Skipping or Nonsense-Associated Altered Splicing
Title of the book
Retinal Degenerative Diseases
Author(s)
Barny Iris, Perrault Isabelle, Rio Marlène, Dollfus Hélène, Defoort-Dhellemmes Sabine, Kaplan Josseline, Rozet Jean-Michel, Gerard Xavier
Publisher
Springer International Publishing
ISBN
9783030273774
9783030273781
ISSN
0065-2598
2214-8019
ISSN-L
0065-2598
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
1185
Pages
189-195
Language
english
Abstract
CEP290 mutations cause a spectrum of ciliopathies, including Leber congenital amaurosis. Milder retinal diseases have been ascribed to exclusion of CEP290 mutant exons through basal exon skipping (BES) and/or nonsense-associated altered splicing (NAS). Here, we report two siblings with some preserved vision despite biallelism for presumably severe CEP290 mutations: a maternal splice site change in intron 18 (c.1824 + 3A > G) and a paternal c.6869dup (p.Asn2290Lysfs∗6) in exon 50 that introduces a premature termination codon (PTC) within the same exon. Analyzing mRNAs from fibroblasts of the two siblings, we detected no BES or NAS which could have enabled the production of PTC-free CEP290 isoforms from the paternal allele. In contrast, we reveal partial alteration of exon 18 donor splice site, allowing the transcription of some correctly spliced CEP290 mRNAs from the maternal allele which likely account for the mild retinal disease. This observation adds further variability to the mechanisms underlying CEP290 pleiotropy.
Keywords
Basal exon skipping, CEP290, Early-onset severe retinal dystrophy, Hypomorphic variant, Leber congenital amaurosis, Mild retinal dystrophy, Splicing modulation, Spontaneous exon skipping
Pubmed
Web of science
Create date
03/01/2020 21:35
Last modification date
13/12/2023 7:11
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