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DC Field | Value | Language |
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dc.contributor.author | Borg, Rebecca M. | - |
dc.contributor.author | Farrugia Wismayer, Maia | - |
dc.contributor.author | Bonavia, Karl | - |
dc.contributor.author | Farrugia Wismayer, Andrew | - |
dc.contributor.author | Vella, Malcolm | - |
dc.contributor.author | Vugt, Joke J.F.A. van | - |
dc.contributor.author | Kenna, Brendan J. | - |
dc.contributor.author | Kenna, Kevin P. | - |
dc.contributor.author | Vassallo, Neville | - |
dc.contributor.author | Veldink, Jan H. | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.date.accessioned | 2022-02-04T18:23:48Z | - |
dc.date.available | 2022-02-04T18:23:48Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Borg, R., Farrugia, Wismayer, M., Bonavia, K., Farrugia, Wismayer, A., Vella, M., van Vugt J. J.F. A., Kenna, B. J., Kenna, K. P., Vassallo, N., Veldink, J. H., & Cauchi, R. J. (2021). Genetic analysis of ALS cases in the isolated island population of Malta. European Journal of Human Genetics, 29(4), 604-614. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/88348 | - |
dc.description.abstract | Genetic isolates are compelling tools for mapping genes of inherited disorders. The archipelago of Malta, a sovereign microstate in the south of Europe is home to a geographically and culturally isolated population. Here, we investigate the epidemiology and genetic profile of Maltese patients with amyotrophic lateral sclerosis (ALS), identified throughout a 2-year window. Cases were largely male (66.7%) with a predominant spinal onset of symptoms (70.8%). Disease onset occurred around mid-age (median age: 64 years, men; 59.5 years, female); 12.5% had familial ALS (fALS). Annual incidence rate was 2.48 (95% CI 1.59-3.68) per 100,000 person-years. Male-to-female incidence ratio was 1.93:1. Prevalence was 3.44 (95% CI 2.01-5.52) cases per 100,000 inhabitants on 31st December 2018. Whole-genome sequencing allowed us to determine rare DNA variants that change the protein-coding sequence of ALS-associated genes. Interestingly, the Maltese ALS patient cohort was found to be negative for deleterious variants in C9orf72, SOD1, TARDBP or FUS genes, which are the most commonly mutated ALS genes globally. Nonetheless, ALS-associated repeat expansions were identified in ATXN2 and NIPA1. Variants predicted to be damaging were also detected in ALS2, DAO, DCTN1, ERBB4, SETX, SCFD1 and SPG11. A total of 40% of patients with sporadic ALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene, whilst the genetic cause of two thirds of fALS cases could not be pinpointed to known ALS genes or risk loci. This warrants further studies to elucidate novel genes that cause ALS in this unique population isolate. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Adulthood -- Malta | en_GB |
dc.subject | Age factors in disease -- Malta | en_GB |
dc.subject | Older people -- Malta | en_GB |
dc.subject | Amyotrophic lateral sclerosis -- Malta | en_GB |
dc.subject | Gene frequency | en_GB |
dc.subject | Mutation (Biology) -- Research | en_GB |
dc.subject | Isolating mechanisms | en_GB |
dc.title | Genetic analysis of ALS cases in the isolated island population of Malta | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1038/s41431-020-00767-9 | - |
dc.publication.title | European Journal of Human Genetics | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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