Matrin 3 variants are frequent in Italian ALS patients

Marangi, Giuseppe; Lattante, Serena; Doronzio, Paolo Niccolò; Conte, Amelia; Tasca, Giorgio; Monforte, Mauro; Patanella, Agata Katia; Bisogni, Giulia; Meleo, Emiliana; Spada, Salvatore La; Zollino, Marcella; Sabatelli, Mario

doi:10.1016/j.neurobiolaging.2016.09.023

Cited by 37 publications

(31 citation statements)

References 23 publications

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“…Exome sequencing in an unresolved kindred identified cosegregating missense mutations in MATR3 [10]. Across studies, MATR3 missense mutations were observed in 0.5%-2% of ALS patients (Table 2) [10,[48][49][50][51][52][53]. While in the discovery family, multiple patients were diagnosed with ALS and dementia [10], so far MATR3 was not screened in FTD patents.…”

Section: Matr3mentioning

confidence: 99%

ALS Genes in the Genomic Era and their Implications for FTD

2018

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Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.

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Section: Matr3mentioning

confidence: 99%

ALS Genes in the Genomic Era and their Implications for FTD

2018

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“…13,14 Recently, mutations in MATR3 were identified as a cause of FALS 15 and were also detected in SALS. 16,17 In that report, densely stained nuclei of motor neurons and glial cells by MATR3 immunostaining were described as a pathologic finding associated with SALS cases; MATR3positive NCIs were not observed in FALS or SALS cases, except in one patient harboring C9orf72 hexanucleotide repeat expansion. Moreover, MATR3 has not been detected in TDP-43epositive NCIs.…”

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confidence: 90%

Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis

Tada

Doi

Koyano

et al. 2018

The American Journal of Pathology

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Mutations in the MATR3 gene have been identified as a cause of familial amyotrophic lateral sclerosis, but involvement of the matrin 3 (MATR3) protein in sporadic amyotrophic lateral sclerosis (SALS) pathology has not been fully assessed. We immunohistochemically analyzed MATR3 pathology in the spinal cords of SALS and control autopsy specimens. MATR3 immunostaining of the motor neuron nuclei revealed two distinct patterns: mild and strong staining. There were no differences in the ratio of mild versus strong nuclear staining between the SALS and control cases. MATR3-containing neuronal cytoplasmic inclusions (NCIs) were observed in 60% of SALS cases. Most motor neurons with MATR3-positive NCIs exhibited a mild nuclear staining pattern. Although 16.8% of NCIs positive for transactivating response region DNA-binding protein 43 (TDP-43) were estimated as double-labeled by MATR3, no MATR3-positive or TDP-43-negative NCIs were observed. Although a previous study found that MATR3-positive NCIs are present only in cases with C9orf72 hexanucleotide repeat expansion, ubiquitin-positive granular NCIs were not observed in the cerebellum, which have been reported as specific to C9orf72-related ALS. Six ALS cases were confirmed to be negative for the GGGGCC hexanucleotide. Our results reveal that MATR3 is a component of TDP-43-positive NCIs in motor neurons, even in SALS, and indicate the broader involvement of MATR3 in ALS pathology and the heterogeneity of TDP-43-positive NCIs.

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“…After reading the full text, we excluded 20 out of 34 studies clearly not meeting our inclusion criteria (Table ). Finally, 14 papers 35‐48 met the inclusion criteria and were included in our evaluation (Figure 1). Of the selected papers, only 2 studies 39,48 aimed to evaluate the primary research question of determining whether NGS is more accurate than Sanger sequencing to identify pathological mutations of ALS‐associated genes.…”

Section: Resultsmentioning

confidence: 99%

“…In 13 studies, 35‐47 NGS allowed to identify already known mutations in 21 genes, and new or rare variants in 27 genes (Figure 3). Identified variants were nonsense or missense mutations leading to a frameshift mutation resulting in a truncated protein and a loss of protein function.…”

Section: Resultsmentioning

confidence: 99%

The NGS technology for the identification of genes associated with the ALS. A systematic review

Pecoraro

Mandrioli

Carone

et al. 2020

Eur J Clin Investigation

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Background: More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and groundbreaking tool to identify disease-associated variants. Despite documented advantages of NGS, its diagnostic reliability needs to be addressed in order to use this technology for specific routine diagnosis. Material and Methods: Literature database was explored to identify studies comparing NGS and Sanger sequencing for the detection of variants causing ALS. We collected data about patients' characteristics, disease type and duration, NGS and Sanger properties. Results: More than 200 bibliographic references were identified, of which only 14 studies matching our inclusion criteria. Only 2 out of 14 studies compared results of NGS analysis with the Sanger sequencing. Twelve studies screened causative genes associated to ALS using NGS technologies and confirmed the identified variants with Sanger sequencing. Overall, data about more 2,000 patients were analysed. The number of genes that were investigated in each study ranged from 1 to 32, the most frequent being FUS, OPTN, SETX and VCP. NGS identified already known mutations in 21 genes, and new or rare variants in 27 genes. Conclusions: NGS seems to be a promising tool for the diagnosis of ALS in routine clinical practice. Its advantages are represented by an increased speed and a lowest sequencing cost, but patients' counselling could be problematic due to the discovery of frequent variants of unknown significance. K E Y W O R D S amyothrophic lateral sclerosis, evidence, gene detection, next-generation sequencing, systematic review 2 of 16 | PECORARO Et Al. 4 of 16 | PECORARO Et Al.duration, site of onset); (d) characteristics of NGS technologies; (e) investigated outcomes as defined above.

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Matrin 3 variants are frequent in Italian ALS patients

Cited by 37 publications

References 23 publications

ALS Genes in the Genomic Era and their Implications for FTD

ALS Genes in the Genomic Era and their Implications for FTD

Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis

The NGS technology for the identification of genes associated with the ALS. A systematic review

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