A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy

Conforti, Francesca Luisa; Sprovieri, T.; Mazzei, R.; Ungaro, C; Bella, Vincenzo La; Tessitore, Alessandro; Patitucci, A; Magariello, A.; Gabriele, A. L.; Tedeschi, Gioacchino; Simone, I. L.; Majorana, G.; Valentino, Paola; Condino, Francesca; Bono, Francesco; Monsurrò, Maria Rosaria; Muglia, M.; Quattrone, Aldo

doi:10.1016/j.nmd.2007.07.003

Cited by 47 publications

(36 citation statements)

References 6 publications

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“…This substitution was observed in 2% of Italian controls, and thus it may represent a rare polymorphism. 11 In our meta-analysis, we found a frequency of 0.2% for this polymorphism in apparently healthy individuals, which is in the range of the estimated life span incidence of ALS (1/800). It may be possible that this mutation is associated in some populations with other genetic variations, modulating its effect.…”

Section: Resultsmentioning

confidence: 52%

“…This G434A mutation is rare; to date, it has been found in only 1 of 3155 patients with ALS, including our results and all published data. 5,[10][11][12] The fact that it has not been observed in 2135 healthy individuals suggests that T T T T T T T T T T T G R R A a C C C C C c T T T T T T R A it is not a neutral polymorphism. However, functional studies will be necessary to confirm this theory.…”

Section: Resultsmentioning

confidence: 99%

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Mutations of the ANG Gene in French Patients With Sporadic Amyotrophic Lateral Sclerosis

Paubel

Violette²,

Amy³

et al. 2008

Arch Neurol

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Background: Mutations in the angiogenin gene, ANG, have been associated recently with familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown.Objective: To assess the frequency of ANG gene mutations in 855 French patients with sporadic ALS. Design: We analyzed by direct sequencing the full coding region of the ANG gene in a cohort of French patients with sporadic ALS. The clinical characteristics of patients carrying ANG mutations are detailed. Setting: French ALS Study Group. Patients: A total of 855 patients with sporadic ALS. Main Outcome Measures: Results of genetic analyses.

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Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Mutations of the ANG Gene in French Patients With Sporadic Amyotrophic Lateral Sclerosis

Paubel

Violette²,

Amy³

et al. 2008

Arch Neurol

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“…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.…”

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confidence: 54%

Extensive genetics of ALS

Chiò

Calvo²,

Mazzini³

et al. 2012

Neurology

146

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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

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“…More importantly, loss-of-function mutations have been found in patients with ALS and PD (Conforti et al, 2008;Gellera et al, 2008;Greenway et al, 2006;Paubel et al, 2008;van Es et al, 2009;Wu et al, 2007). ANG is the only 'loss-of-function' mutated gene identified in ALS.…”

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confidence: 99%

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

Pizzo

Sarcinelli

Sheng

et al. 2013

Journal of Cell Science

100

112

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SummaryAngiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stressinduced small RNA (tiRNA), which reprograms protein translation into a survival mechanism. The ribonucleolytic activity of ANG is essential for both processes but how this activity is regulated is unknown. We report here that ribonuclease/angiogenin inhibitor 1 (RNH1) controls both the localization and activity of ANG. Under growth conditions, ANG is located in the nucleus and is not associated with RNH1 so that the ribonucleolytic activity is retained to ensure rRNA transcription. Cytoplasmic ANG is associated with and inhibited by RNH1 so that random cleavage of cellular RNA is prevented. Under stress conditions, ANG is localized to the cytoplasm and is concentrated in stress granules where it is not associated with RNH1 and thus remains enzymatically active for tiRNA production. By contrast, nuclear ANG is associated with RNH1 in stressed cells to ensure that the enzymatic activity is inhibited and no unnecessary rRNA is produced to save anabolic energy. Knockdown of RNH1 abolished stress-induced relocalization of ANG and decreased cell growth and survival.

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A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy

Cited by 47 publications

References 6 publications

Mutations of the ANG Gene in French Patients With Sporadic Amyotrophic Lateral Sclerosis

Mutations of the ANG Gene in French Patients With Sporadic Amyotrophic Lateral Sclerosis

Extensive genetics of ALS

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

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