A novel heterozygous SETX mutation in a patient presenting with chorea and motor neuron disease

Saracchi, Enrico; Castelli, Marianna; Bassi, Maria Teresa; Brighina, Erika; Cereda, Diletta; Marzorati, L.; Patassini, Mirko; Appollonio, Ildebrando; Ferrarese, Carlo; Brighina, Laura

doi:10.3109/21678421.2013.865751

Cited by 8 publications

(12 citation statements)

References 7 publications

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“…Our study further widens the geographic range for the origin of disease‐causing heterozygous missense mutations of the SETX gene, which have already been implicated in ALS in patients from different countries (Avemaria et al., ; Hirano et al., ; Kenna et al., ; Saracchi et al., ). To the best of our knowledge, our study is the first demonstrating a novel SETX mutation in the Hungarian ALS population (Table ).…”

Section: Discussionmentioning

confidence: 59%

“…To date, only 17 pathogenic SETX mutations (Figure ) have been implicated in the development of the autosomal dominant juvenile form, ALS4. The typical phenotype, present in the majority of the ALS4 patients, presents as a combination of lower and upper motor neuron impairments (Avemaria et al., ; Hirano et al., ; Saracchi et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…The 17 known heterozygous missense mutations of the SETX gene are located in exons 1, 5, 8, 11, 12, 13, 17, and 24 (Table ). Four of the 17 mutations are located within the helicase domain of the SETX protein (Chen et al., ; Hirano et al., ; Kenna et al., ; Saracchi et al., ). In AOA2, homozygous or compound heterozygous missense mutations located within the helicase domain are generally associated with less severe phenotypes than the mutations affecting other regions of the protein (Anheim et al., ; Moreira et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been demonstrated that, in AOA2, missense mutations affecting the N‐terminal or the helicase domain of SETX cause phenotypes similar to those caused by deletions, nonsense, or frameshift mutations (Chen et al., ). However, only missense SETX mutations have been implicated in the development of ALS4, to date (Avemaria et al., ; Hirano et al., ; Kenna et al., ; Saracchi et al., ); deletions, nonsense, frameshift, or other types of mutations have not yet been detected for this disease (Table ).…”

Section: Discussionmentioning

confidence: 99%

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High‐throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

et al. 2017

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BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of the motor neurons. To date, 126 genes have been implicated in ALS. Therefore, the heterogenous genetic background of ALS requires comprehensive genetic investigative approaches.MethodsIn this study, DNA from 28 Hungarian ALS patients was subjected to targeted high‐throughput sequencing of the coding regions of three Mendelian ALS genes: FUS, SETX, and C9ORF72.ResultsA novel heterozygous missense mutation (c.791A>G, p.N264S) of the SETX gene was identified in a female patient presenting an atypical ALS phenotype, including adult onset and lower motor neuron impairment. No further mutations were detected in the other Mendelian ALS genes investigated.ConclusionOur study contributes to the understanding of the genetic and phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest that the elucidation of the genetic background of MNDs requires a complex approach, including the screening of both Mendelian and non‐Mendelian genes.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High‐throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

et al. 2017

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“…So far, the T3I, L389S, T1118I, C1554G, K2018E, K2029E, R2136H, and I2547T mutations in the SETX gene have been identified in both patients with FALS and those with SALS with widely differing symptoms (Additional file 1 : Table S1). In a recent report, a patient with late onset ALS4, bulbar involvement, and predominantly proximal distribution of amyotrophy presented with choreic movements and elevated alpha-fetoprotein levels [ 14 ]. In contrast, one study demonstrated that previously published ALS4-related missense mutations are most likely to be non-pathogenic and just polymorphisms [ 15 ].…”

Section: Classification Of Hereditary Alsmentioning

confidence: 99%

Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis

Yamashita

Ando

2015

Transl Neurodegener

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Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is characterized by neuronal loss and degeneration of the upper motor neurons (UMNs) and lower motor neurons (LMNs), and is usually fatal due to respiratory failure within 3–5 years of onset. Although approximately 5–10 % of patients with ALS have an inherited form of the disease, the distinction between hereditary and apparently sporadic ALS (SALS) seems to be artificial. Thus, genetic factors play a role in all types of ALS, to a greater or lesser extent. During the decade of upheaval, the evolution of molecular genetics technology has rapidly advanced our genetic knowledge about the causes of ALS, and the relationship between the genetic subtypes and clinical phenotype. In this review, we will focus on the possible genotype-phenotype correlation in hereditary ALS. Uncovering the identity of the genetic factors in ALS will not only improve the accuracy of ALS diagnosis, but may also provide new approaches for preventing and treating the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s40035-015-0036-y) contains supplementary material, which is available to authorized users.

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R Loops and Links to Human Disease

Richard

Manley

2017

Journal of Molecular Biology

175

133

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Aberrant R-loop structures are increasingly being realized as an important contributor to human disease. R loops, which are mainly co-transcriptional, abundant RNA/DNA hybrids, form naturally and can indeed be beneficial for transcription regulation at certain loci. However, their unwanted persistence elsewhere or in particular situations can lead to DNA double-strand breaks, chromosome rearrangements, and hypermutation, which are all sources of genomic instability. Mutations in genes involved in R-loop resolution or mutations leading to R-loop formation at specific genes affect the normal physiology of the cell. We discuss here the examples of diseases for which a link with R loops has been described, as well as how disease-causing mutations might participate in the development and/or progression of diseases that include repeat-associated conditions, other neurological disorders, and cancers.

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A novel heterozygous SETX mutation in a patient presenting with chorea and motor neuron disease

Cited by 8 publications

References 7 publications

High‐throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

High‐throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis

R Loops and Links to Human Disease

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