4.5 Article

Genetic analysis of ALS cases in the isolated island population of Malta

期刊

EUROPEAN JOURNAL OF HUMAN GENETICS
卷 29, 期 4, 页码 604-614

出版社

SPRINGERNATURE
DOI: 10.1038/s41431-020-00767-9

关键词

-

资金

  1. University of Malta Research Excellence Fund
  2. Malta Council for Science & Technology Internationalisation Partnership Award
  3. EMBO short-term fellowship
  4. Bjorn Formosa Scholarship for Advanced Research into ALS/MND - non-profit organisation, ALS Malta Foundation
  5. Endeavour Scholarship (Malta)
  6. EU-European Social Fund under Operational Programme II-Cohesion Policy 2014-2020, Investing in human capital to create more opportunities and promote the well-being of society

向作者/读者索取更多资源

Genetic isolates like the Maltese population are useful for mapping genes related to inherited disorders like ALS. The Maltese ALS patients are predominantly male, with spinal onset of symptoms, and onset age around mid-age. While some patients have rare genetic variants associated with ALS, the genetic cause of many fALS cases in this population remains unknown. Further studies are needed to discover novel genes causing ALS in this unique genetic isolate.
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 31(st) 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据