6533b7d7fe1ef96bd12685ad
RESEARCH PRODUCT
ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion
A ChiòG MoraM SabatelliC CaponnettoC LunettaB. J TraynorJ. O JohnsonM. A NallsA CalvoC MogliaG BorgheroF TrojsiV La BellaP VolantiI SimoneF SalviF. O LogulloN RivaP CarreraF GianniniJ MandrioliR TanelM CapassoL TremolizzoS BattistiniM. R MurruP OrigoneM ZollinoS PencoL MazziniS D'alfonsoG RestagnoM BrunettiM BarberisF. L ConfortiG LogroscinoI BartolomeiG MancardiP MandichK MarinouR SideriL MoscaG Lauria PinterM CorboN FiniA FasanoA ArosioC FerrareseG TedeschiM. R MonsurròG PiccirilloC FemianoA BersanoL CorradoA BagarottiR SpataroT CollettiA ConteM LuigettiS LattanteG MarangiM SantarelliA PetrucciC RicciM BenigniF CasaleG MarraliG FudaI OssolaS CammarosanoA IlardiU ManeraD BertuzzoR TanelF PisanoE CostantinoC PaniR PudduC CareddaV PirasS TranquilliS CuccuD CorongiuM MelisA MiliaF MarrosuM. G MarrosuG FlorisA CannasS CuccuS TranquilliA TiccaM PugliattiA PirisiL. D ParishP OcchineriE OrtuT. B CauD Loisubject
Male0301 basic medicineAgingC9ORF72Genetic Association Studie030105 genetics & heredityBiologySettore MED/03 - GENETICA MEDICA03 medical and health sciences0302 clinical medicineC9orf72medicineAlleleAmyotrophic lateral sclerosisAmyotrophic lateral sclerosiAgedAtaxin-2Regulator geneAmyotrophic lateral sclerosis; ATXN2; C9ORF72; Phenotype; Neuroscience (all); Medicine (all); Aging; Developmental Biology; Geriatrics and Gerontology; Neurology (clinical)GeneticsDNA Repeat ExpansionNeuroscience (all)ProteinMedicine (all)General NeuroscienceATXN2Middle AgedDNA Repeat Expansionmedicine.diseaseAmyotrophic lateral sclerosis3. Good healthC9orf72 ProteinAmyotrophic lateral sclerosis; ATXN2; C9ORF72; Phenotype; Neurology (clinical); Neuroscience (all); Aging; Developmental Biology; Geriatrics and GerontologyPhenotypeItalyPopulation studyFemaleSettore MED/26 - NeurologiaNeurology (clinical)Geriatrics and GerontologyTrinucleotide repeat expansion030217 neurology & neurosurgeryHumanDevelopmental Biologydescription
Abstract There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non- C9ORF72 mutated patients.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 |