IRCCS Oasi Maria SS

Troina, Italy

IRCCS Oasi Maria SS

Troina, Italy
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Lambert J.-C.,French Institute of Health and Medical Research | Lambert J.-C.,University of Lille Nord de France | Sleegers K.,Neurodegenerative Brain Diseases Group | Sleegers K.,University of Antwerp | And 81 more authors.
Journal of Alzheimer's Disease | Year: 2010

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene. © 2010 IOS Press and the authors. All rights reserved.

Haveman M.,TU Dortmund | Perry J.,University of Cardiff | Salvador-Carulla L.,University of Cádiz | Walsh P.N.,University College Dublin | And 11 more authors.
Journal of Intellectual and Developmental Disability | Year: 2011

Background POMONA II was a European Commission public health-funded project. The research questions in this article focus on age-specific differences relating to environmental and lifestyle factors, and the 17 medical conditions measured by the POMONA Checklist of Health Indicators (P15). Method The P15 was completed in a cross-sectional design for a stratified sample of 1,253 adults with ID across 14 European member states. Results Older people (55+) were more likely to live in larger residential homes. Rates of smoking and use of alcohol were lower than in the general population but were higher with older age. More than 60% of older adults had a sedentary lifestyle. Cataract, hearing disorder, diabetes, hypertension, osteoarthritis/arthrosis, and osteoporosis were positively associated with advancing age; allergies and epilepsy, negatively associated. Conclusions Some evidence of health disparities was found for older people with ID, particularly in terms of underdiagnosed or inadequately managed preventable health conditions. © 2011 Australasian Society for the Study of Intellectual Disability, Inc.

Miceli F.,University of Naples Federico II | Striano P.,University of Genoa | Soldovieri M.V.,University of Molise | Fontana A.,University of Palermo | And 9 more authors.
Epilepsia | Year: 2015

Mutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early onset epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic electroencephalography (EEG) and neuroradiologic features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early onset epilepsy and neurocognitive deficits segregated with a novel mutation in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity. © Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Genin E.,French Institute of Health and Medical Research | Genin E.,University Paris Diderot | Hannequin D.,French Institute of Health and Medical Research | Hannequin D.,Center National Of Reference Maladie Dalzheimer Du Sujet Jeune | And 63 more authors.
Molecular Psychiatry | Year: 2011

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease. © 2011 Macmillan Publishers Limited All rights reserved.

Barone R.,University of Catania | Carrozzi M.,Institute for Maternal and Child Health | Parini R.,San Gerardo Hospital | Battini R.,IRCCS Stella Maris | And 14 more authors.
Journal of Neurology | Year: 2015

PMM2-CDG (PMM2 gene mutations) is the most common congenital disorder of N-glycosylation. We conducted a nationwide survey to characterize the frequency, clinical features, glycosylation and genetic correlates in Italian patients with PMM2-CDG. Clinical information was obtained through a questionnaire filled in by the referral physicians including demographics, neurological and systemic features, neuroimaging data and genotype. Glycosylation analyses of serum transferrin were complemented by MALDI-Mass Spectrometry (MALDIMS). Between 1996 and 2012, data on 37 Italian patients with PMM2-CDG were collected. All the patients with a severe phenotype were unable to walk unaided, 84 % had severe intellectual disability and 81 % microcephaly. Conversely, among 17 mildly affected patients 82 % had independent ambulation, 64 % had borderline to mild intellectual disability and 35 % microcephaly. Epilepsy and stroke-like events did not occur among patients with the mild phenotype. The rate and extent of systemic involvement were more pronounced in severely affected patients. The L32R misfolding mutation of the PMM2 gene occurred in 70 % of the patients with the mild phenotype and was associated with a less severe underglycosylation of serum Tf at MALDI-MS analyses. Despite their different disease severity, all patients had progressive (olivo)pontocerebellar atrophy that was the hallmark clinical feature for the diagnosis. A mild neurological phenotype of PMM2- CDG marked by preserved ambulatory ability and autonomy and associated with L32R mutation is particularly frequent in Italy. PMM2-CDG should be considered in patients with even mild developmental disability and/or unexplained progressive cerebellar atrophy. © Springer-Verlag Berlin Heidelberg 2014.

Falsaperla R.,University of Catania | Pavone L.,University of Catania | Fichera M.,IRCCS Oasi Maria SS | Striano P.,University of Genoa | Pavone P.,University of Catania
European Journal of Paediatric Neurology | Year: 2012

Males with methyl-CpG-binding protein 2 (MECP2) mutations may present with neonatal encephalopathy. We report on an infant with a MECP2 mutation who exhibited complex constellation of symptoms, including severe hypotonia, respiratory failure, and apneic episodes. In the neonatal period these symptoms are common to other disorders, including Ondine syndrome. Our observation confirms that the triad of severe hypotonia, apneic episodes, and respiratory failure may be caused by MECP2 mutations. Neonatologist and neuropediatricians must be alert to the presence of these symptoms to exclude this rare but severe disorder. Clinical suspicion and molecular confirmation of MECP2 mutation is of great importance for defining the diagnosis of this rare affection. © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Prandini P.,University of Verona | Pasquali A.,University of Verona | Malerba G.,University of Verona | Marostica A.,University of Verona | And 59 more authors.
Psychiatric Genetics | Year: 2012

Objective The objective of this study was to replicate an association study on a newly collected Italian autism spectrum disorder (ASD) cohort by studying the genetic markers associated with ASDs from recent genome-wide and candidate gene association studies. Methods We have genotyped 746 individuals from 227 families of the Italian Autism Network using allelic discrimination TaqMan assays for seven common single-nucleotide polymorphisms: rs2292813 (SLC25A12 gene), rs35678 (ATP2B2 gene), rs4307059 (between CDH9 and CDH10 genes), rs10513025 (between SEMA5A and TAS2R1 genes), rs6872664 (PITX1 gene), rs1861972 (EN2 gene), and rs4141463 (MACROD2 gene). A family-based association study was conducted. Results A significant association was found for two of seven markers: rs4307059 T allele (odds ratio: 1.758, SE = 0.236; P-value = 0.017) and rs35678 TC genotype (odds ratio: 0.528, SE = 0.199; P-value = 0.0013). Conclusion A preferential allele transmission of two markers located at loci previously associated with social and verbal communication skill has been confirmed in patients of a new ASD family sample. Psychiatr Genet 00:000-000. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

D'Antoni S.,CNR Institute of Neurological Sciences | Spatuzza M.,CNR Institute of Neurological Sciences | Bonaccorso C.M.,IRCCS Oasi Maria SS | Musumeci S.A.,IRCCS Oasi Maria SS | And 5 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2014

Activation of group-I metabotropic glutamate receptors, mGlu1 and mGlu5, triggers a variety of signalling pathways in neurons and glial cells, which are differently implicated in synaptic plasticity. The earliest and much of key studies discovered abnormal mGlu5 receptor function in Fragile X syndrome (FXS) mouse models which then motivated more recent work that finds mGlu5 receptor dysfunction in related disorders such as intellectual disability (ID), obsessive-compulsive disorder (OCD) and autism. Therefore, mGlu1/5 receptor dysfunction may represent a common aetiology of these complex diseases. Furthermore, many studies have focused on dysregulation of mGlu5 signalling to synaptic protein synthesis. However, emerging evidence finds abnormal mGlu5 receptor interactions with its scaffolding proteins in FXS which results in mGlu5 receptor dysfunction and phenotypes independent of signalling to protein synthesis. Finally, both an increased and reduced mGlu5 functioning seem to be associated with ID and autism spectrum disorders, with important consequences for potential treatment of these developmental disorders. © 2014 Elsevier Ltd.

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