Clinical characteristics and genetic analysis of a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to compound heterozygous variants of RRM2B gene.
10.3760/cma.j.cn511374-20201116-00799
- VernacularTitle:RRM2B基因复合杂合变异导致的线粒体耗竭综合征家系的临床特征和遗传学分析
- Author:
Yanhong WANG
1
;
Xuan ZHENG
;
Xiangdie WANG
;
Xiaoman ZHANG
;
Pengbo GUO
;
Lei LIU
;
Shiyue MEI
Author Information
1. Henan Provincial Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory for Children's Genetic and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Provincial Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450018, China. xiaomay2008@163.com.
- Publication Type:Journal Article
- MeSH:
Cell Cycle Proteins;
Child;
China;
DNA, Mitochondrial/genetics*;
Female;
Genetic Testing;
Humans;
Infant;
Mutation;
Pedigree;
Ribonucleotide Reductases;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2022;39(1):26-30
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A).
METHODS:Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein.
RESULTS:The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants.
CONCLUSION:The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.
