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 a...

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Main Authors: Fei Gao, Katherine R Schon, Jana Vandrovcova, Özlem Yayıcı Köken, Sharika Raga, Kireshnee Naidu, Maryke Schoonen, Nimita Rani, Pedro Tomaselli, Dipti Baskar, Musambo Kapapa, Ipek Polat, Lindsay A Wilson, Kumarasamy Thangaraj, Uluç Yiş, Bevinahalli N Nandeesh, David Bearden, Michelle Kvalsund, Franclo Henning, Seena Vengalil, Atchayaram Nalini, Claudia F. R. Sobreira, Wilson Marques, Haluk Topoloğlu, Michael G Hanna, Sireesha Yareeda, Venugopalan Y Vishnu, Francois H van derWesthuizen, Izelle Smuts, Surita Meldau, Jo Wilmshurst, Büşranur Çavdarlı, Jeannine Heckmann, Patrick F Chinnery, Rita Horvath
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.52141
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author Fei Gao
Katherine R Schon
Jana Vandrovcova
Özlem Yayıcı Köken
Sharika Raga
Kireshnee Naidu
Maryke Schoonen
Nimita Rani
Pedro Tomaselli
Dipti Baskar
Musambo Kapapa
Ipek Polat
Lindsay A Wilson
Kumarasamy Thangaraj
Uluç Yiş
Bevinahalli N Nandeesh
David Bearden
Michelle Kvalsund
Franclo Henning
Seena Vengalil
Atchayaram Nalini
Claudia F. R. Sobreira
Wilson Marques
Haluk Topoloğlu
Michael G Hanna
Sireesha Yareeda
Venugopalan Y Vishnu
Francois H van derWesthuizen
Izelle Smuts
Surita Meldau
Jo Wilmshurst
Büşranur Çavdarlı
Jeannine Heckmann
Patrick F Chinnery
Rita Horvath
author_facet Fei Gao
Katherine R Schon
Jana Vandrovcova
Özlem Yayıcı Köken
Sharika Raga
Kireshnee Naidu
Maryke Schoonen
Nimita Rani
Pedro Tomaselli
Dipti Baskar
Musambo Kapapa
Ipek Polat
Lindsay A Wilson
Kumarasamy Thangaraj
Uluç Yiş
Bevinahalli N Nandeesh
David Bearden
Michelle Kvalsund
Franclo Henning
Seena Vengalil
Atchayaram Nalini
Claudia F. R. Sobreira
Wilson Marques
Haluk Topoloğlu
Michael G Hanna
Sireesha Yareeda
Venugopalan Y Vishnu
Francois H van derWesthuizen
Izelle Smuts
Surita Meldau
Jo Wilmshurst
Büşranur Çavdarlı
Jeannine Heckmann
Patrick F Chinnery
Rita Horvath
author_sort Fei Gao
collection DOAJ
description 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.
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publishDate 2025-08-01
publisher Wiley
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series Annals of Clinical and Translational Neurology
spelling doaj-art-f7596a1fa3f84524a6ae1cb520ee4e332025-08-20T03:41:54ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-08-011281680168810.1002/acn3.52141Mitochondrial DNA disorders in neuromuscular diseases in diverse populationsFei Gao0Katherine R Schon1Jana Vandrovcova2Özlem Yayıcı Köken3Sharika Raga4Kireshnee Naidu5Maryke Schoonen6Nimita Rani7Pedro Tomaselli8Dipti Baskar9Musambo Kapapa10Ipek Polat11Lindsay A Wilson12Kumarasamy Thangaraj13Uluç Yiş14Bevinahalli N Nandeesh15David Bearden16Michelle Kvalsund17Franclo Henning18Seena Vengalil19Atchayaram Nalini20Claudia F. R. Sobreira21Wilson Marques22Haluk Topoloğlu23Michael G Hanna24Sireesha Yareeda25Venugopalan Y Vishnu26Francois H van derWesthuizen27Izelle Smuts28Surita Meldau29Jo Wilmshurst30Büşranur Çavdarlı31Jeannine Heckmann32Patrick F Chinnery33Rita Horvath34Department of Clinical Neurosciences University of Cambridge Cambridge UKDepartment of Clinical Neurosciences University of Cambridge Cambridge UKUCL Queen Square Institute of Neurology, University College London London UKDepartment of Pediatric Neurology, Faculty of Medicine Akdeniz University Antalya TurkeyDivision of Paediatric Neurology, Department of Paediatrics and Child Health Red Cross War Memorial Children's Hospital Cape Town South AfricaNeurology Research Group, Division of Neurology, Department of Medicine University of Cape Town Cape Town South AfricaFocus Area for Human Metabolomics North‐West University Potchefstroom South AfricaDepartment of Neurology All India Institute of Medical Sciences (AIIMS) Delhi IndiaDepartment of Neuroscience Clinical Hospital of Ribeirão Preto Medical School of, University of São Paulo São Paulo BrazilDepartment of Neurology National Institute of Mental Health & Neurosciences (NIMHANS) Bengaluru IndiaDepartment of Physiotherapy, School of Health Sciences University of Zambia, University Teaching Hospital Neurology Research Office Lusaka ZambiaIzmir Biomedicine and Genome Center (IBG) Izmir TurkeyUCL Queen Square Institute of Neurology, University College London London UKCSIR—Centre for Cellular and Molecular Biology (CCMB) Hyderabad Telangana IndiaPediatric Neurology Department, Faculty of Medicine Dokuz Eylül University Izmir TurkeyDepartment of Neuropathology National Institute of Mental Health & Neurosciences (NIMHANS) Bengaluru IndiaDepartment of Neurology University of Rochester Rochester New York USADepartment of Neurology University of Rochester Rochester New York USADivision of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South AfricaDepartment of Neurology National Institute of Mental Health & Neurosciences (NIMHANS) Bengaluru IndiaDepartment of Neurology National Institute of Mental Health & Neurosciences (NIMHANS) Bengaluru IndiaDepartment of Neuroscience Clinical Hospital of Ribeirão Preto Medical School of, University of São Paulo São Paulo BrazilDepartment of Neuroscience Clinical Hospital of Ribeirão Preto Medical School of, University of São Paulo São Paulo BrazilYeditepe University Hospitals Istanbul TurkeyUCL Queen Square Institute of Neurology, University College London London UKNizam's Institute of Medical Sciences (NIMS) Hyderabad Telangana IndiaDepartment of Neurology All India Institute of Medical Sciences (AIIMS) Delhi IndiaFocus Area for Human Metabolomics North‐West University Potchefstroom South AfricaDepartment of Paediatrics, Steve Biko Academic Hospital University of Pretoria Pretoria South AfricaDivision of Chemical Pathology, Department of Pathology University of Cape Town Medical Faculty Cape Town South AfricaDivision of Paediatric Neurology, Department of Paediatrics and Child Health Red Cross War Memorial Children's Hospital Cape Town South AfricaDepartment of Medical Genetics Ankara Bilkent City Hospital Ankara TurkeyNeuroscience Institute, University of Cape Town Cape Town South AfricaDepartment of Clinical Neurosciences University of Cambridge Cambridge UKDepartment of Clinical Neurosciences University of Cambridge Cambridge UKAbstract 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.https://doi.org/10.1002/acn3.52141
spellingShingle Fei Gao
Katherine R Schon
Jana Vandrovcova
Özlem Yayıcı Köken
Sharika Raga
Kireshnee Naidu
Maryke Schoonen
Nimita Rani
Pedro Tomaselli
Dipti Baskar
Musambo Kapapa
Ipek Polat
Lindsay A Wilson
Kumarasamy Thangaraj
Uluç Yiş
Bevinahalli N Nandeesh
David Bearden
Michelle Kvalsund
Franclo Henning
Seena Vengalil
Atchayaram Nalini
Claudia F. R. Sobreira
Wilson Marques
Haluk Topoloğlu
Michael G Hanna
Sireesha Yareeda
Venugopalan Y Vishnu
Francois H van derWesthuizen
Izelle Smuts
Surita Meldau
Jo Wilmshurst
Büşranur Çavdarlı
Jeannine Heckmann
Patrick F Chinnery
Rita Horvath
Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
Annals of Clinical and Translational Neurology
title Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
title_full Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
title_fullStr Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
title_full_unstemmed Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
title_short Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
title_sort mitochondrial dna disorders in neuromuscular diseases in diverse populations
url https://doi.org/10.1002/acn3.52141
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