Genetic analysis of amyotrophic lateral sclerosis in the Slovenian population

Vrabec, Katarina; Koritnik, Blaž; Leonardis, Lea; Dolenc‐Grošelj, Leja; Zidar, Janez; Smith, Bradley N.; Vance, Caroline; Shaw, Christopher E.; Rogelj, Boris; Glavač, Damjan; Ravnik‐Glavač, Metka

doi:10.1016/j.neurobiolaging.2014.11.011

Cited by 11 publications

(7 citation statements)

References 25 publications

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“…54.5% (6/11) patients had definite, 27.3% (3/11) had a probable, and 18.2% (2/11) had a possible ALS diagnosis according to revised El Escorial criteria 40 . Genetic analyses were previously performed for 54.5% (6/11) patients, with no known ALS related mutations discovered 41 . 18.2% (2/11) patients had a family history of the disease.…”

Section: Resultsmentioning

confidence: 99%

Differential expression of microRNAs and other small RNAs in muscle tissue of patients with ALS and healthy age-matched controls

Kovanda

Leonardis

Zidar

et al. 2018

Sci Rep

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Amyotrophic lateral sclerosis is a late-onset disorder primarily affecting motor neurons and leading to progressive and lethal skeletal muscle atrophy. Small RNAs, including microRNAs (miRNAs), can serve as important regulators of gene expression and can act both globally and in a tissue-/cell-type-specific manner. In muscle, miRNAs called myomiRs govern important processes and are deregulated in various disorders. Several myomiRs have shown promise for therapeutic use in cellular and animal models of ALS; however, the exact miRNA species differentially expressed in muscle tissue of ALS patients remain unknown. Following small RNA-Seq, we compared the expression of small RNAs in muscle tissue of ALS patients and healthy age-matched controls. The identified snoRNAs, mtRNAs and other small RNAs provide possible molecular links between insulin signaling and ALS. Furthermore, the identified miRNAs are predicted to target proteins that are involved in both normal processes and various muscle disorders and indicate muscle tissue is undergoing active reinnervation/compensatory attempts thus providing targets for further research and therapy development in ALS.

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Section: Resultsmentioning

confidence: 99%

Differential expression of microRNAs and other small RNAs in muscle tissue of patients with ALS and healthy age-matched controls

Kovanda

Leonardis

Zidar

et al. 2018

Sci Rep

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“…Thirty-one patients were treated with rulizol, and 37 patients were not yet treated. Seven patients had genetic changes (Vrabec et al, 2015 ), including four patients with a hexanucleotide repeat expansion mutation (HREM) in the C9ORF72 gene, one patient with a mutation in the SOD1 gene (p.Val14Met), and one patient with a mutation in the SOD1 gene (p.Gly93Cys) together with a synonymous alteration c.990A>G (p.Leu330Leu) in TARDBP , and in one patient, we detected a synonymous substitution in the FUS gene (c.1566G>A, p.Arg522Arg).…”

Section: Methodsmentioning

confidence: 99%

“…miRNA pathway disruptions could be a cause or consequence of ALS pathology, which is underlain with altered RNA and protein metabolism, cytotoxicity due to faulty glutamate clearance, the inflammatory response, and neuromuscular junction impairments (Paez-Colasante et al, 2015 ). In addition, in several studies differential expression of miRNAs in ALS have been reported (De Felice et al, 2012 ; Cloutier et al, 2015 ; Vrabec et al, 2015 ; Chen et al, 2016 ).…”

Section: Introductionmentioning

confidence: 98%

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Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients

Vrabec

Boštjančič

Koritnik

et al. 2018

Front. Mol. Neurosci.

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Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM). In addition, as recent studies connected AATK and frontotemporal dementia (FTD) and DNM2 and hereditary spastic paraplegia (HSP), these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M), CNM, and ALS, thus opening future research toward a better understanding of the cell biology involved in these partly overlapping pathologies.

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“…68 In an international cross-sectional study evaluating 4448 ALS patients, 37% of individuals with FALS are in possession of this mutation, having as many as 700-1600 copies of the repeat sequence compared to controls who only have 23 copies. 69 Comparable studies have been conducted in French (46% FALS, 8% SALS), 70 Italian (46% FALS), 71 Greek (50% FALS, 8.2% SALS), 72 Turkish (18.3% FALS, 3.1% SALS), 73 Slavic (5.9% SALS), 74 and Russian (15% FALS, 2.5% SALS) 75 populations testing positive for the GGGGCC repeat. Studies on Chinese SALS populations have yielded results indicating this sequence is not correlated to their patient populations, potentially describing a predilection for the C9orf72 hexanucleotide repeat for Caucasians.…”

Section: Chromosome 9 Open Reading Frame 72 (C9orf72) Hexanucleotide mentioning

confidence: 99%

Cross-Sectional Survey of Relevant Literatures as to the Current Proposed Disease Mechanisms and Treatments of Amyotrophic Lateral Sclerosis (ALS)

Sanford¹

2015

MJM

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Genetic analysis of amyotrophic lateral sclerosis in the Slovenian population

Cited by 11 publications

References 25 publications

Differential expression of microRNAs and other small RNAs in muscle tissue of patients with ALS and healthy age-matched controls

Differential expression of microRNAs and other small RNAs in muscle tissue of patients with ALS and healthy age-matched controls

Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients

Cross-Sectional Survey of Relevant Literatures as to the Current Proposed Disease Mechanisms and Treatments of Amyotrophic Lateral Sclerosis (ALS)

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