Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
Loading...
Date
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
Neuromuscular features are common in mitochondrial DNA (mtDNA) disorders. The genetic architecture of mtDNA disorders in diverse populations is poorly understood. We analysed mtDNA variants from whole-exome sequencing data in neuromuscular patients from South Africa, Brazil, India, Turkey and Zambia. In 998 individuals, there were two definite diagnoses, two possible diagnoses and eight secondary findings. Surprisingly, common pathogenic mtDNA variants found in people of European ancestry were very rare. Whole-exome or -genome sequencing from undiagnosed patients with neuromuscular symptoms should be re-analysed for mtDNA variants, but the landscape of pathogenic mtDNA variants differs around the world.
Description
DATA AVAILABILITY STATEMENT : At the end of the study, participants de-identified exome and genome data will be archived in the European Molecular Biology Laboratory European Bioinformatics Institute’s European Genome-Phenome Archive (EMBL EBI EGA), with community access to this and selected deidentified REDCap data managed via an ICGNMD Data Access Committee.
SUPPLEMENTARY MATERIALS : FIGURE S1. Overall mtDNA coverage by centre. The x‐axis shows the position along the mitochondrial chromosome and the y‐axis shows the depth of coverage. Each coloured line represents an individual participant. Two distinct patterns of coverage can be observed. South Africa, Zambia and Brazil used the same sequencing provider and show similar patterns of coverage. FIGURE S2. Scatterplot showing sequencing depth at position m.3243 and age at recruitment. The x‐axis shows the age at recruitment and the y‐axis shows sequencing depth at position m.3243. The dots represent individual participants. The red horizontal line is at sequencing depth 20 and the green vertical line is at age 15 years. There were 231 children aged <15 years with sequencing depth >20, 85 children aged <15 years with sequencing depth ≤20, 407 individuals aged ≥15 years with sequencing depth >20 and 275 individuals aged ≥15 years with sequencing depth ≤20. FIGURE S3. Number of variants were identified in individuals from different countries. The y‐axis shows the total number of variants found in an individual. Individual results are shown with dots which are coloured according to the individual's haplogroup. Across different centres, high number of variants are observed in people with L0 and L1 haplogroups. TABLE S1. Numbers of individuals with each haplogroup by country.
SUPPLEMENTARY MATERIALS : FIGURE S1. Overall mtDNA coverage by centre. The x‐axis shows the position along the mitochondrial chromosome and the y‐axis shows the depth of coverage. Each coloured line represents an individual participant. Two distinct patterns of coverage can be observed. South Africa, Zambia and Brazil used the same sequencing provider and show similar patterns of coverage. FIGURE S2. Scatterplot showing sequencing depth at position m.3243 and age at recruitment. The x‐axis shows the age at recruitment and the y‐axis shows sequencing depth at position m.3243. The dots represent individual participants. The red horizontal line is at sequencing depth 20 and the green vertical line is at age 15 years. There were 231 children aged <15 years with sequencing depth >20, 85 children aged <15 years with sequencing depth ≤20, 407 individuals aged ≥15 years with sequencing depth >20 and 275 individuals aged ≥15 years with sequencing depth ≤20. FIGURE S3. Number of variants were identified in individuals from different countries. The y‐axis shows the total number of variants found in an individual. Individual results are shown with dots which are coloured according to the individual's haplogroup. Across different centres, high number of variants are observed in people with L0 and L1 haplogroups. TABLE S1. Numbers of individuals with each haplogroup by country.
Keywords
Neuromuscular, Mitochondrial DNA (mtDNA), Patients, Diagnoses
Sustainable Development Goals
SDG-03: Good health and well-being
Citation
Gao, F., Schon, K.R., Vandrovcova, J. et al. 2025, 'Mitochondrial DNA disorders in neuromuscular diseases in diverse populations', Annals of clinical and translational neurology, vol. 12, no. 8, pp. 1680-1688. DOI: 10.1002/acn3.52141.