Ibanez, Kristina;
Jadhav, Bharati;
Zanovello, Matteo;
Gagliardi, Delia;
Clarkson, Christopher;
Facchini, Stefano;
Garg, Paras;
... Tucci, Arianna; + view all
(2024)
Increased frequency of repeat expansion mutations across different populations.
Nature Medicine
10.1038/s41591-024-03190-5.
(In press).
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Abstract
Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions and technological limitations leading to underascertainment. Here, leveraging whole-genome sequencing data from 82,176 individuals from different populations, we found an overall disease allele frequency of REDs of 1 in 283 individuals. Modeling disease prevalence using genetic data, age at onset and survival, we show that the expected number of people with REDs would be two to three times higher than currently reported figures, indicating underdiagnosis and/or incomplete penetrance. While some REDs are population specific, for example, Huntington disease-like 2 in Africans, most REDs are represented in all broad genetic ancestries (that is, Europeans, Africans, Americans, East Asians and South Asians), challenging the notion that some REDs are found only in specific populations. These results have worldwide implications for local and global health communities in the diagnosis and counseling of REDs.
| Type: | Article |
|---|---|
| Title: | Increased frequency of repeat expansion mutations across different populations |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41591-024-03190-5 |
| Publisher version: | http://dx.doi.org/10.1038/s41591-024-03190-5 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, SPINOCEREBELLAR ATAXIAS, FRONTOTEMPORAL DEMENTIA, HUNTINGTONS-DISEASE, CLINICAL-FEATURES, PREVALENCE, ALLELES, ONSET, PENETRANCE, DISORDERS, AGE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10199283 |
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