» Articles » PMID: 10721666

Mitochondrial DNA Mutations in Leigh Syndrome and Their Phylogenetic Implications

Overview
Journal J Hum Genet
Specialty Genetics
Date 2000 Mar 18
PMID 10721666
Citations 13
Authors
Affiliations
Soon will be listed here.
Abstract

Of 100 patients with the clinical diagnosis of Leigh syndrome, 21 were found to have specific enzyme defects: 15 involving cytochrome c oxidase (COX); 4, pyruvate dehydrogenase complex (PDHC); one, complex I (reduced nicotinamide adenine dinucleotide [NADH]-coenzyme Q reductase) and one, complex II (succinate-ubiquinone reductase) deficiencies. In addition to the most common form of COX deficiency, mtDNA mutations in the adenosine triphosphatase (ATPase) 6 coding region were also commonly seen. Eighteen patients (18%) had mtDNA mutations at nucleotide position (np) 8993 or 9176. The mutated DNAs were present in a heteroplasmic state, comprising more than 90% of the DNA in muscle and/or blood samples from all patients. Patients with the T-to-G mutation at np 8993 usually had early onset of the disease with rapid progression, showing the typical clinical features of Leigh syndrome. On the other hand, those with the T-to-C 8993 mutation showed a milder and more chronic course. Patients with the mutation at np 9176 showed variable courses. Phylogenetic analysis of mtDNA D-loop sequences for the patients with the ATPase 6 mutations and normal Japanese subjects revealed that a T-to-G/C mutation at np 8993 and a T-to-C mutation at np 9176 occurred many times independently in the Japanese population.

Citing Articles

Syndromic Retinitis Pigmentosa: A Narrative Review.

Janaky M, Braunitzer G Vision (Basel). 2025; 9(1.

PMID: 39846623 PMC: 11755594. DOI: 10.3390/vision9010007.


A systematic review on the biochemical threshold of mitochondrial genetic variants.

Smith K, Moreira J, Wilson C, Padera J, Lamason A, Xue L Genome Res. 2024; 34(3):341-365.

PMID: 38627095 PMC: 11067886. DOI: 10.1101/gr.278200.123.


Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review.

Dawod P, Jancic J, Marjanovic A, Brankovic M, Jankovic M, Samardzic J Diagnostics (Basel). 2021; 11(11).

PMID: 34829316 PMC: 8620769. DOI: 10.3390/diagnostics11111969.


Serial cryoFIB/SEM Reveals Cytoarchitectural Disruptions in Leigh Syndrome Patient Cells.

Zhu Y, Sun D, Schertel A, Ning J, Fu X, Gwo P Structure. 2020; 29(1):82-87.e3.

PMID: 33096015 PMC: 7802768. DOI: 10.1016/j.str.2020.10.003.


Mitochondrial DNA heteroplasmy in disease and targeted nuclease-based therapeutic approaches.

Nissanka N, Moraes C EMBO Rep. 2020; 21(3):e49612.

PMID: 32073748 PMC: 7054667. DOI: 10.15252/embr.201949612.