53 research outputs found
A genome-wide scan for common alleles affecting risk for autism
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 Ă 10â8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 Ă 10â8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C
The Genetic Landscape and Epidemiology of Phenylketonuria
Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]â1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A>G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C>T (p.Arg408Trp) (22.2%), c.1066â11G>A (IVS10â11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066â11G>A];[1066â11G>A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.Fil: Hillert, Alicia. No especifĂca;Fil: Anikster, Yair. No especifĂca;Fil: Belanger Quintana, Amaya. No especifĂca;Fil: Burlina, Alberto. No especifĂca;Fil: Burton, Barbara K.. No especifĂca;Fil: Carducci, Carla. No especifĂca;Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada". FundaciĂłn de EndocrinologĂa Infantil. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada"; ArgentinaFil: Christodoulou, John. No especifĂca;Fil: Dordevic, Maja. No especifĂca;Fil: Desviat, Lourdes R.. No especifĂca;Fil: Eliyahu, Aviva. No especifĂca;Fil: Evers, Roeland A.F.. No especifĂca;Fil: Fajkusova, Lena. No especifĂca;Fil: Feillet, Francois. No especifĂca;Fil: Bonfim Freitas, Pedro E.. No especifĂca;Fil: Gizewska, MarĂa. No especifĂca;Fil: Gundorova, Polina. No especifĂca;Fil: Karall, Daniela. No especifĂca;Fil: Kneller, Katya. No especifĂca;Fil: Kutsev, Sergey I.. No especifĂca;Fil: Leuzzi, Vincenzo. No especifĂca;Fil: Levy, Harvey L.. No especifĂca;Fil: Lichter Koneck, Uta. No especifĂca;Fil: Muntau, Ania C.. No especifĂca;Fil: Namour, Fares. No especifĂca;Fil: Oltarzewsk, Mariusz. No especifĂca;Fil: Paras, Andrea. No especifĂca;Fil: Perez, BelĂ©n. No especifĂca;Fil: Polak, Emil. No especifĂca;Fil: Polyakov, Alexander V.. No especifĂca;Fil: Porta, Francesco. No especifĂca;Fil: Rohrbach, Marianne. No especifĂca;Fil: Scholl BĂŒrgi, Sabine. No especifĂca;Fil: SpĂ©cola, Norma. No especifĂca;Fil: Stojiljkovic, Maja. No especifĂca;Fil: Shen, Nan. No especifĂca;Fil: Santana da Silva, Luiz C.. No especifĂca;Fil: Skouma, Anastasia. No especifĂca;Fil: van Spronsen, Francjan. No especifĂca;Fil: Stoppioni, Vera. No especifĂca;Fil: Thöny, Beat. No especifĂca;Fil: Trefz, Friedrich K.. No especifĂca;Fil: Vockley, Jerry. No especifĂca;Fil: Yu, Youngguo. No especifĂca;Fil: Zschocke, Johannes. No especifĂca;Fil: Hoffmann, Georg F.. No especifĂca;Fil: Garbade, Sven F.. No especifĂca;Fil: Blau, Nenad. No especifĂca
The Genetic Landscape and Epidemiology of Phenylketonuria
Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A gt G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C gt T (p.Arg408Trp) (22.2%), c.1066-11G gt A (IVS10-11G gt A) (6.4%), and c.782G gt A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G gt A];[1066-11G gt A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome
The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism
All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di SanitĂ . The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country
Attention-deficit/hyperactivity disorder drugs and growth: an Italian prospective observational study.
EâH Bond Activation Reactions (E = H, C, Si, Ge) at Ruthenium: Terminal Phosphides, Silylenes, and Germylenes
Misurare lâintelligenza fluida in bambini con autismo: il contributo della Scala Leiter-3 e delle Matrici di Raven- Forma Colore (CPM)
Lo studio esamina il contributo della Leiter-3 e delle CPM, test cultural-free non verbali, nellâassessment dellâintelligenza fluida in individui con disturbo dello spettro autistico (ASD), che frequentemente presentano una compromissione del linguaggio. Le prestazioni di 18 bambini con ASD (78% M, EtĂ media: 7;6; range 4,8 â 11,4) bilanciati per etĂ e genere con bambini a sviluppo tipico (ST), hanno mostrato differenze non significative rispetto al gruppo di controllo alle CPM (ASD: 57° vs. ST: 76° percentile, p=.169), di contro a differenze significative alla Leiter-3 (QI non Verbale: 87 vs. 104, p<.001; Memoria non Verbale: 79 vs. 101, p<.001; VelocitĂ di Elaborazione: 76 vs. 102, p<.001). Da correlazioni distinte per gruppo emergono significative positive associazioni nel gruppo ASD tra gli indici della Leiter-3 e il QI alle CPM (QI non Verbale: .783***; Memoria non Verbale: .679**; VelocitĂ di Elaborazione: .496*), mentre nessuna associazione significativa nei bambini con ST: .213; .347; -.171
Misurare l'intelligenza fluida in bambini con autismo: confronto tra prestaioni alla Scala Leiter-3 e alla Matrici di Raven Forma Colore (CPM)
Il disturbo dello spettro autistico comporta specifiche disfunzioni nella capacitĂ di comprensione degli stati mentali e affettivi, di simbolizzazione e comunicazione. Pertanto, una corretta valutazione dellâintelligenza fluida, in questa popolazione clinica, potrebbe risultare difficoltosa e la scelta dello strumento determinante. La Scala Leiter-3 e le CPM sembrano test particolarmente idonei a valutare lâintelligenza fluida negli individui con autismo in quanto richiedono entrambi risposte non verbali, pur differenziandosi nella procedura di somministrazione, solo parzialmente non verbale nelle CPM. Uno studio pilota su bambini con sviluppo tipico (Ferrandes & Pierucci, 2017), ha mostrato una discreta validitĂ concorrente tra i due strumenti (gli indici di Q.I. generale e Q.I. equivalente, rispettivamente, correlano in modo significativo com un buon effect size: r=.406**). Il presente contributo ha inteso esplorare la concordanza o eventuale differenza tra le misure di intelligenza in un gruppo di bambini con disturbo dello spettro autistico rispetto ad un gruppo di controllo
Geographical epidemiology of neonatal transitory hypothyroidism. Trend evidence in central Italian region
Acido Valproico: analisi statistica applicata al monitoraggio del farmaco totale e libero
Atti del VII corso di aggiornamento in neuropsichiatria infantile, Fan
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