Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 09 2019
03 09 2019
Historique:
received:
25
04
2019
accepted:
15
08
2019
entrez:
5
9
2019
pubmed:
5
9
2019
medline:
21
10
2020
Statut:
epublish
Résumé
X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5. In XLAS cases suspected of being caused by aberrant splicing, transcript analysis needs to be conducted to determine splicing patterns and assess the pathogenicity. However, such analysis is not always available. We conducted a functional splicing assay using a hybrid minigene for seven COL4A5 intronic mutations: one was identified by us and six were found in the Human Gene Mutation Database. The minigene assay revealed exon skipping in four variants, exon skipping and a 10-bp insertion in one variant, and no change in one variant, which appeared not to be pathogenic. For one variant, our assay did not work. The results of all three cases for which transcript data were available were consistent with our assay results. Our findings may help to increase the accuracy of genetic test results and clarify the mechanisms causing aberrant splicing.
Identifiants
pubmed: 31481700
doi: 10.1038/s41598-019-48990-9
pii: 10.1038/s41598-019-48990-9
pmc: PMC6722096
doi:
Substances chimiques
COL4A5 protein, human
0
Collagen Type IV
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12696Références
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