The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation
- Tseng, Y.T., Li, S.W., HuangFu, W.C., Yen, Y., Liu, I.H.
- Molecular genetics & genomic medicine 8(11): e1497 (Journal)
- Registered Authors
- Tseng, Yen-Tzu
- MeSH Terms
- Cell Cycle Proteins/genetics*
- Cell Cycle Proteins/metabolism
- Loss of Function Mutation*
- Mitochondrial Diseases/genetics*
- Muscular Dystrophies/genetics*
- Point Mutation
- Ribonucleotide Reductases/genetics*
- Ribonucleotide Reductases/metabolism
- 32931159 Full text @ Mol Genet Genomic Med
Tseng, Y.T., Li, S.W., HuangFu, W.C., Yen, Y., Liu, I.H. (2020) The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation. Molecular genetics & genomic medicine. 8(11):e1497.
Background Mitochondrial DNA maintenance defects (MDMDs) is one of the critical pediatric dysfunction. One of the recent report indicated that a severe patient of MDMDs carries the NP_056528.2:p.Asn221Ser (N221S) variation in the RRM2B gene (NM_015713.5). However, there is no direct evidence demonstrating the nature of the N221S variation.
Materials and methods This study aimed to utilize zebrafish and morpholino oligomer (MO) knockdown technique to provide direct evidence for the nature of the N221S variation in the RRM2B.
Results The results showed that two distinct MOs were both able to perturb the expression of rrm2b in zebrafish and dose-dependently induced morphological defects. Furthermore, co-injection of human wild-type RRM2B mRNA with MO-e4i4 successfully rescued the developmental defects, whereas co-injection of RRM2B/N221S mRNA with MO-e4i4 did not rescue the developmental defects.
Conclusion In conclusion, the functional assay in this study provided the direct evidence proving that the N221S variation is a loss-of-function mutation and plausibly related to the pathogenic developmental defects found in the infants of previous clinical reports.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes