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LAMB2 novel variant c.2885-9 C>A affects RNA splicing in a minigene assay.
- Source :
-
Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 Jul; Vol. 9 (7), pp. e1704. Date of Electronic Publication: 2021 May 13. - Publication Year :
- 2021
-
Abstract
- Background: Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants.<br />Methods: Using high-throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885-9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta-2 in kidney tissues.<br />Results: Two novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885-9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885-9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta-2, the protein encoded by LAMB2.<br />Conclusion: We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2.<br /> (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
- Subjects :
- Diagnosis, Differential
Female
Genetic Testing methods
HEK293 Cells
Humans
Infant
Laminin metabolism
Myasthenic Syndromes, Congenital diagnosis
Nephrotic Syndrome diagnosis
Point Mutation
Pupil Disorders diagnosis
Laminin genetics
Myasthenic Syndromes, Congenital genetics
Nephrotic Syndrome genetics
Pupil Disorders genetics
RNA Splicing
Subjects
Details
- Language :
- English
- ISSN :
- 2324-9269
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Molecular genetics & genomic medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33982833
- Full Text :
- https://doi.org/10.1002/mgg3.1704