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Case report: Altered pre-mRNA splicing caused by intronic variant c.1499 + 1G > A in the SLC4A4 gene
- Source :
- Frontiers in Pediatrics. 10
- Publication Year :
- 2022
- Publisher :
- Frontiers Media SA, 2022.
-
Abstract
- Proximal renal tubular acidosis (pRTA) with ocular abnormalities is an autosomal recessive disease caused by variants in the Solute Carrier Family 4 Member 4 (SLC4A4) gene. Patients present with metabolic acidosis and low plasma bicarbonate concentration (3∼17 mmol/L). In addition, they are often accompanied by ocular abnormalities, intellectual disability, and growth retardation. The patient underwent whole exome sequencing (WES) and bioinformatics analysis of variant pathogenicity in this study. Then, a minigene assay was conducted to analyze the splicing site variant further. Compound heterozygous variants in the SLC4A4 gene (NM_003759.3), c.145C > T (p.Arg49*) and c.1499 + 1G > A, were detected by WES. The minigene assay showed an mRNA splicing aberration caused by the c.1499 + 1G > A variant. Compared with the wild type, the mutant type caused 4-base insertion between exons 10 and 11 of SLC4A4 after expression in HEK293 cells. In conclusion, the c.1499 + 1G > A variant in the SLC4A4 gene may be one of the genetic causes in the patient. Moreover, our study provides the foundation for future gene therapy of such pathogenic variants.
- Subjects :
- Pediatrics, Perinatology and Child Health
Subjects
Details
- Language :
- English
- ISSN :
- 22962360
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pediatrics
- Accession number :
- edsair.doi.dedup.....db710549bbfeab1e46e7832681be8d9a
- Full Text :
- https://doi.org/10.3389/fped.2022.890147