Back to Search Start Over

Case report: Altered pre-mRNA splicing caused by intronic variant c.1499 + 1G > A in the SLC4A4 gene

Authors :
Yan Liu
Wenchao Sheng
Jinying Wu
Jie Zheng
Xiufang Zhi
Shuyue Zhang
Chunyu Gu
Detong Guo
Wenhong Wang
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.

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