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Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1.
- Source :
-
Journal of Clinical Medicine . Jan2023, Vol. 12 Issue 2, p473. 10p. - Publication Year :
- 2023
-
Abstract
- Cerebral adrenoleukodystrophy (CALD) is a fatal genetic disease characterized by rapid, devastating neurological decline, with a narrow curative treatment window in the early stage. Non-canonical splice-site (NCSS) variants can easily be missed during genomic DNA analyses, and only a few of them in ABCD1 have been explored. Here, we studied a Chinese patient with clinical features similar to those of early-stage CALD but with a negative molecular diagnosis and a sibling who had presumably died of CALD. Trio-based whole-exome sequencing (trio-WES) and RNA sequencing (RNA-Seq) revealed a novel hemizygote NCSS variant c.901-25_901-9 del in ABCD1 intron 1, resulting in a complex splicing pattern. The in vitro minigene assay revealed that the c.901-25_901-9 del construct contained two aberrant transcripts that caused skipping of exon 2 and a small 48-bp deletion on left of the same exon. We identified a novel NCSS variant, that extends the spectrum of the known ABCD1 variants, and demonstrated the pathogenicity of this gene variant. Our findings highlight the importance of combining RNA-Seq and WES techniques for prompt diagnosis of leukodystrophy with NCSS variants. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20770383
- Volume :
- 12
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 161478498
- Full Text :
- https://doi.org/10.3390/jcm12020473