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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Neuromuscular disease genetics in under-represented populations: increasing data diversity
Brain, Volume 146, No. 12, Year 2023
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Description
Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally. © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
Authors & Co-Authors
Wilson, Lindsay A.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Perry, Luke Daniel
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Record, Christopher J.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Schon, Katherine R.
United Kingdom, Cambridge
University of Cambridge
Raga, Sharika V.
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Red Cross War Memorial Children's Hospital
Naidu, Kireshnee
South Africa, Cape Town
University of Cape Town
South Africa, Stellenbosch
Stellenbosch University
Polat, Ayse Ipek
Turkey, Izmir
Dokuz Eylül Üniversitesi
Kapapa, Musambo M.
Zambia, Lusaka
University Teaching Hospital Lusaka
Dominik, Natalia
United Kingdom, London
Ucl Queen Square Institute of Neurology
Efthymiou, Stephanie
United Kingdom, London
Ucl Queen Square Institute of Neurology
Nel, Melissa
South Africa, Cape Town
University of Cape Town
Fassad, Mahmoud R.
United Kingdom, Newcastle
Newcastle University
Schoonen, Maryke
South Africa, Potchefstroom
North-west University
Jonvik, Hallgeir
United Kingdom, London
Ucl Queen Square Institute of Neurology
Lubbe, Elsa
South Africa, Pretoria
University of Pretoria
Vengalil, Seena
India, Bengaluru
National Institute of Mental Health and Neuro Sciences
Töpf, Ana
United Kingdom, Newcastle
Newcastle University
Steyn, Elizabeth Christina
South Africa, Cape Town
University of Cape Town
Mahungu, Amokelani C.
South Africa, Cape Town
University of Cape Town
Ceylan, Ahmet Cevdet
Turkey, Ankara
Ankara Bilkent City Hospital
Turkey, Ankara
Ankara Yildirim Beyazit University
Tallapaka, Karthik Bharadwaj
India, Hyderabad
Centre for Cellular and Molecular Biology India
Nandeesh, Bevinahalli Nanjegowda
India, Bengaluru
National Institute of Mental Health and Neuro Sciences
Wa-Somwe, Somwe V.
Zambia, Lusaka
University of Lusaka
Bearden, David R.
Zambia, Lusaka
University of Zambia
United States, Rochester
University of Rochester Medical Center
Kvalsund, Michelle P.
United States, Rochester
University of Rochester Medical Center
Zambia, Lusaka
University of Zambia School of Medicine
Ramdharry, Gita M.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Yiş, Uluç
Turkey, Izmir
Dokuz Eylül Üniversitesi
Sárközy, Anna
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Bugiardini, Enrico
United Kingdom, London
Ucl Queen Square Institute of Neurology
Henning, F.
South Africa, Stellenbosch
Stellenbosch University
Wilmshurst, J. Madeleine
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Red Cross War Memorial Children's Hospital
Heckmann, Jeannine M.
South Africa, Cape Town
University of Cape Town
McFarland, Robert
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Taylor, Robert William
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Smuts, Izelle
South Africa, Pretoria
University of Pretoria
Van Der Westhuizen, F. H.
South Africa, Potchefstroom
North-west University
Marques, Wilson J.
Brazil, Sao Paulo
Universidade de São Paulo
Bhatia, Rohit S.
India, New Delhi
All India Institute of Medical Sciences, new Delhi
Nalini, Atchayaram
India, Bengaluru
National Institute of Mental Health and Neuro Sciences
Thangaraj, Kumarasamy
India, Hyderabad
Centre for Cellular and Molecular Biology India
Straub, V. W.
United Kingdom, Newcastle
Newcastle University
Horvàth, Rita
United Kingdom, Cambridge
University of Cambridge
Chinnery, Patrick Francis
United Kingdom, Cambridge
University of Cambridge
Pitceathly, Robert D.S.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Muntoni, Francesco M.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Houlden, Henry H.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Vandrovcova, J.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Reilly, Mary M.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Hanna, Michael G.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Statistics
Authors: 49
Affiliations: 27
Identifiers
Doi:
10.1093/brain/awad254
ISSN:
00068950
Research Areas
Disability
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study
Study Approach
Qualitative
Study Locations
South Africa
Zambia