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Updated: Oct 12, 2025
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study
Yuqing Shi1, Guohong Chen2, Dan Sun3
1Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Abstract:
Mitochondrial DNA (mtDNA) associated mitochondrial diseases hold a crucial position but comprehensive and systematic studies are relatively rare. Among the 262 patients of four children's hospitals in China, 96%-point mutations (30 alleles in 11 genes encoding tRNA, rRNA, Complex I and V) and 4%-deletions (seven of ten had not been reported before) were identified as the cause of 14 phenotypes. MILS presented the highest genetic heterogeneity, while the m.3243A > G mutation was the only "hotspot" mutation with a wide range of phenotypes. The degrees of heteroplasmy in the leukocytes of MM were higher than MELAS. The heteroplasmy level of patients was higher than that in mild and carrier group, while we found low-level heteroplasmy pathogenic mutations as well. Some homoplasmic variations (e.g., m.9176 T > C mutation) are having high incomplete penetrance. For a suspected MELAS, m.3243A > G mutation was recommended to detect first; while for a suspected LS, trios-WES and mtDNA genome sequencing by NGS were recommended first in both blood and urine.
Insights
Mitochondrial DNA (mtDNA) point mutations and deletions cause various mitochondrial diseases in children. Specific mutations like m.3243A>G are common, while others show incomplete penetrance.
Area of Science:
- Genetics
- Molecular Biology
- Pediatrics
Background:
- Mitochondrial DNA (mtDNA) diseases are significant but understudied.
- Comprehensive genetic analysis is crucial for diagnosis and understanding disease mechanisms.
Purpose of the Study:
- To systematically investigate the genetic causes of mitochondrial diseases in Chinese children.
- To identify common and novel mtDNA mutations and deletions and their associated phenotypes.
Main Methods:
- Genetic analysis of 262 pediatric patients from four Chinese children's hospitals.
- Identification of point mutations and deletions in mtDNA genes.
- Next-generation sequencing (NGS) and whole exome sequencing (WES) were utilized.
Main Results:
- 96% of patients had point mutations (30 alleles in 11 genes) and 4% had deletions (7 novel).
- Mitochondrial myopathy, lactic acidosis, and stroke-like episodes (MELAS) showed high genetic heterogeneity.
- The m.3243A>G mutation was a hotspot, linked to diverse phenotypes; heteroplasmy levels varied by condition and tissue.
Conclusions:
- mtDNA mutations are a major cause of pediatric mitochondrial diseases in China.
- Diagnostic strategies should prioritize specific mutations (e.g., m.3243A>G for MELAS) and consider NGS for complex cases.
- Understanding heteroplasmy and incomplete penetrance is key for accurate diagnosis and genetic counseling.
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