Genetic landscape of ALS in Malta based on a quinquennial analysis

Wismayer, Maia Farrugia; Wismayer, Andrew Farrugia; Borg, Rebecca; Bonavia, Karl; Abela, Andre; Chircop, Charmaine; Aquilina, Josanne; Soler, Doriette; Pace, Adrian; Vella, Malcolm; Vassallo, Neville; Cauchi, Ruben J.

doi:10.1016/j.neurobiolaging.2022.11.011

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…In a Maltese cohort describing 52 ALS patients, 17% of patients were identified to carry the intermediate repeat expansion (vs. 4.5% of healthy control individuals) [ 26 ]. This is the highest rate of ATXN1 intermediate repeat expansion carriers reported, which may be due to the fact that the population of Malta is a relatively secluded island nation.…”

Section: Introductionmentioning

confidence: 99%

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

Nagy,

Pál,

Engelhardt

et al. 2024

BMC Med Genomics

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another. The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors.In this review we aimed to summarize the most widely recognized and studied ALS linked repeat expansions and copy number variations other than the hexanucleotide repeat expansion in the C9orf72 gene. We compare and contrast their involvement and phenotype modifying roles in ALS among different populations.

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Section: Introductionmentioning

confidence: 99%

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

Nagy,

Pál,

Engelhardt

et al. 2024

BMC Med Genomics

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Reduced levels of ALS gene DCTN1 induce motor defects in Drosophila

et al. 2023

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neuromuscular disease that has a strong genetic component. Deleterious variants in the DCTN1 gene are known to be a cause of ALS in diverse populations. DCTN1 encodes the p150 subunit of the molecular motor dynactin which is a key player in the bidirectional transport of cargos within cells. Whether DCTN1 mutations lead to the disease through either a gain or loss of function mechanism remains unresolved. Moreover, the contribution of non-neuronal cell types, especially muscle tissue, to ALS phenotypes in DCTN1 carriers is unknown. Here we show that gene silencing of Dctn1, the Drosophila main orthologue of DCTN1, either in neurons or muscles is sufficient to cause climbing and flight defects in adult flies. We also identify Dred, a protein with high homology to Drosophila Dctn1 and human DCTN1, that on loss of function also leads to motoric impairments. A global reduction of Dctn1 induced a significant reduction in the mobility of larvae and neuromuscular junction (NMJ) deficits prior to death at the pupal stage. RNA-seq and transcriptome profiling revealed splicing alterations in genes required for synapse organisation and function, which may explain the observed motor dysfunction and synaptic defects downstream of Dctn1 ablation. Our findings support the possibility that loss of DCTN1 function can lead to ALS and underscore an important requirement for DCTN1 in muscle in addition to neurons.

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SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis

Cauchi

2023

Neural Regeneration Research

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Genetic landscape of ALS in Malta based on a quinquennial analysis

Cited by 3 publications

References 46 publications

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

Reduced levels of ALS gene DCTN1 induce motor defects in Drosophila

SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis

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