Mitochondrial DNA disorders in neuromuscular diseases in diverse populations

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.

Figure 1

(A) Flow diagram summarising filtering steps applied to 1122 participants from diverse populations who had exome sequencing for investigation of neuromuscular disorders between 2021 and 2023. (B) Number of participants by age. Age ranges from infancy to 86 years with median age of 25 years. (C) Number of probands assigned to each of 14 diagnostic categories. The commonest categories were genetic peripheral neuropathy, limb‐girdle muscular dystrophy and congenital muscular dystrophy or myopathy.

Figure 2

World map showing the countries which recruited study participants and pie charts showing the proportions of the different mitochondrial haplogroups identified in participants from each country. Brazil is shown in yellow, Turkey in purple, South Africa in blue, Zambia in green and India in red.