Clinical phenotype and genetic characteristics of a family with mitochondrial DNA depletion syndrome 8B caused by RRM2B gene mutation
10.3760/cma.j.cn115354-20240824-00503
- VernacularTitle:RRM2B基因变异相关线粒体DNA耗竭综合征8B型一家系临床及遗传学分析
- Author:
Baoyan LI
1
;
Xia LI
;
Li YANG
;
Xin ZHANG
;
Yufen LI
;
Yuzeng HAN
Author Information
1. 临沂市人民医院急诊内科，临沂 276003
- Keywords:
Mitochondrial DNA depletion syndrome;
RRM2B gene;
Variation
- From:
Chinese Journal of Neuromedicine
2024;23(10):999-1005
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical phenotype and genetic characteristics of a family with mitochondrial DNA depletion syndrome (MTDPS8B) caused by RRM2B gene mutation. Methods:Data of a family with MTDPS8B admitted to Department of Pediatric Neurology, Linyi People's Hospital in November 2019 were collected. Whole exome sequencing, mitochondrial loop gene sequencing and Sanger sequencing were used for genetic test in the child and family members, and pathogenicity analysis and protein 3D modeling on the mutation sites were conducted. The clinical phenotype and genetic characteristics of the family members were summarized.Results:Six subjects in these 8 individuals from the three generations of this family underwent genetic test. Four subjects had c.627G>A(p.M209I) (NM_001172477) heterozygous variation in RRM2B gene on the chromosome 8, and the variation was highly conserved; and no report on this variation has been found in domestic and foreign databases yet. Protein 3D modeling found that this variation may affect protein stability and function. The proband (male) and two older sisters carried the same variant had MTDPS8B, manifested as gastrointestinal dysfunction and progressive decline in motor function and intelligence, while the mother carried the same variant only had intellectual disability; the father and eldest sister did not carry the mutation and had normal clinical phenotype; the maternal grandparents had normal clinical phenotype and had passed away without genetic test; variation and disease were isolated in this family. The variation was interpreted as pathogenic (PM1+PM2+PP1+PP3) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. Conclusion:The c.627G>A variant can cause RRM2B gene-related disease, and family members carried the same variants vary in clinical severity.
