@article{fec08eab06b84bf8b308e127905217cf,
title = "The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation",
abstract = "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.",
author = "Tseng, {Yen Tzu} and Li, {Shang Wei} and HuangFu, {Wei Chun} and Yun Yen and Liu, {I. Hsuan}",
note = "Funding Information: The authors thank Dr. Harry J. Mersmann for proof‐reading and grammatically revising this manuscript. This work was financially supported by Ministry of Science and Technology (MOST105‐2628‐B‐002‐005‐MY4 to I‐Hsuan Liu and MOST‐108‐2321‐B‐038‐003 to Yun Yen), Council of Agriculture of Taiwan (108AS‐21.1.7‐AD‐U1[14] to I‐Hsuan Liu), Health and welfare surcharge of tobacco products grant (MOHW108‐TDU‐B‐212‐124014, MOHW108‐TDU‐B‐212‐124026 and MOHW108‐TDU‐B‐212‐124020 to Yun Yen), and also by the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Funding Information: The authors thank Dr. Harry J. Mersmann for proof-reading and grammatically revising this manuscript. This work was financially supported by Ministry of Science and Technology (MOST105-2628-B-002-005-MY4 to I-Hsuan Liu and MOST-108-2321-B-038-003 to Yun Yen), Council of Agriculture of Taiwan (108AS-21.1.7-AD-U1[14] to I-Hsuan Liu), Health and welfare surcharge of tobacco products grant (MOHW108-TDU-B-212-124014, MOHW108-TDU-B-212-124026 and MOHW108-TDU-B-212-124020 to Yun Yen), and also by the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Publisher Copyright: {\textcopyright} 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC",
year = "2020",
doi = "10.1002/mgg3.1497",
language = "English",
volume = "8",
journal = "Molecular Genetics and Genomic Medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",
number = "11",
}