Variations in the coding and regulatory sequences of the angiogenin (ANG) gene are not associated to ALS (amyotrophic lateral sclerosis) in the Italian population

Corrado, Lucia; Battistini, Stefania; Penco, Silvana; Bergamaschi, Laura; Testa, Lucia; Ricci, Claudia; Giannini, F.; Greco, G.; Patrosso, Maria Cristina; Pileggi, Silvana; Causarano, R.; Mazzini, Letizia; Momigliano–Richiardi, Patricia; D’Alfonso, Sandra

doi:10.1016/j.jns.2007.03.009

Cited by 37 publications

(34 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, a recent metaanalysis reported that ANG mutations have been detected in only ϳ0.5% of patients with ALS of European ancestry 36 and the frequency was even lower in Italian patients. [37][38][39][40] Although it remains possible that our cohort was not sufficiently powered to detect ANG mutations, our data confirm that mutations in this gene are not a frequent cause of motor neuron degeneration.…”

mentioning

confidence: 53%

Extensive genetics of ALS

Chiò

Calvo²,

Mazzini³

et al. 2012

Neurology

153

View full text Add to dashboard Cite

Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods:The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed. Results:Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p ϭ 0.001), and age at onset Յ54 years (odds ratio 1.79; p ϭ 0.012). Conclusions:We have found that ϳ11% of patients with ALS carry a genetic mutation, with Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of adult age involving the motor system, with a progressive and invariably fatal course. In 5% of cases it is considered to be genetically transmitted (familial ALS [fALS]) 1,2 while in the remaining cases it occurs sporadically in the population (sporadic ALS [sALS] Several studies have assessed the frequency of mutations of single genes, 11 but few studies have compared relative frequencies of SOD1, TARDBP, ANG, ; all these studies were based on tertiary center series of cases, and were consequently skewed toward a younger population of patients with a larger number of fALS 16 ; moreover, only one of them reported data on C9ORF72, which is now

show abstract

mentioning

confidence: 53%

Extensive genetics of ALS

Chiò

Calvo²,

Mazzini³

et al. 2012

Neurology

153

View full text Add to dashboard Cite

show abstract

“…This toxic formation of protein aggregates applies to many other native and mutated misfolded proteins characterized in ALS patients, like the vesicle associated membrane protein (VAMP)-associated protein (VAPB), TARDBP, FUS, and angiotensin (ANG) genes [33,54], and has been extended by the discovery of frequent combined C9orf72 gene mutations that facilitate native protein aggregation (see below). The recently discovered TBK1 gene mutations modify two main pathways, inflammation and autophagy [55], and may alter microglial adaptation to neuronal damage, in particular the engulfment of dying spinal cord neurons [56].…”

Section: Genetics Of Alsmentioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

View full text Add to dashboard Cite

“…All ALS patients included in the study had been previously screened for SOD1 and Angiogenin (ANG; MIM 105850) gene mutations [Corrado et al, 2007;Gellera et al, 2008]. Control DNA was obtained from 771 unrelated age-and regionallymatched Italian subjects (university and hospital staff, blood donors) with no reported history of neurological disorders.…”

Section: Patients and Controlsmentioning

confidence: 99%

High frequency ofTARDBPgene mutations in Italian patients with amyotrophic lateral sclerosis

et al. 2009

Self Cite

View full text Add to dashboard Cite

Recent studies identified rare missense mutations in amyotrophic lateral sclerosis (ALS) patients in the TARDBP gene encoding TAR DNA binding protein (TDP)-43, the major protein of the ubiquitinated inclusions (UBIs) found in affected motor neurons (MNs). The aim of this study was to further define the spectrum of TARDBP mutations in a large cohort of 666 Italian ALS patients (125 familial and 541 sporadic cases). The entire coding region was sequenced in 281 patients, while in the remaining 385 cases only exon 6 was sequenced. In 18 patients, of which six are familial, we identified 12 different heterozygous missense mutations (nine novel) all locating to exon 6, which were absent in 771 matched controls. The c.1144G>A (p.A382T) variation was observed in seven patients, thus representing the most frequent TARDBP mutation in ALS. Analysis of microsatellites surrounding the TARDBP gene indicated that p.A382T was inherited from a common ancestor in 5 of the 7 patients. Altogether, the frequency of TARDBP gene mutations appears to be particularly high in Italian ALS patients compared to individuals of mainly Northern European origin (2.7% vs. 1%). Western blot analysis of lymphocyte extracts from two patients carrying the p.A382T and p.S393L TARDBP mutations showed the presence of lower molecular weight TDP-43 bands, which were more abundant than observed in healthy controls and patients negative for TARDBP mutations. In conclusion, this report contributes to the demonstration of the causative role of the TARDBP gene in ALS pathogenesis and indicates that mutations may affect the stability of the protein even in nonneuronal tissues.

show abstract

Variations in the coding and regulatory sequences of the angiogenin (ANG) gene are not associated to ALS (amyotrophic lateral sclerosis) in the Italian population

Cited by 37 publications

References 19 publications

Extensive genetics of ALS

Extensive genetics of ALS

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

High frequency ofTARDBPgene mutations in Italian patients with amyotrophic lateral sclerosis

Contact Info

Product

Resources

About