Candidate gene study of HOXB1 in autism spectrum disorder / Lucia A. MUSCARELLA in Molecular Autism, (May 2010)  

Public ISBD [article]  inMolecular Autism > (May 2010) . - 39 p. Titre : Candidate gene study of HOXB1 in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lucia A. MUSCARELLA, Auteur ; Carmela BRAVACCIO, Auteur ; Cindy SCHNEIDER, Auteur ; Monica SACCANI, Auteur ; Carlo LENTI, Auteur ; Roberto MILITERNI, Auteur ; Grazia GIANA, Auteur ; Riccardo ALESSANDRELLI, Auteur ; Barbara MANZI, Auteur ; Roberto SACCO, Auteur ; Vito GUARNIERI, Auteur ; Raun D. MELMED, Auteur ; Paolo CURATOLO, Auteur ; Antonio M. PERSICO, Auteur ; Leonardo D'AGRUMA, Auteur Année de publication : 2010 Article en page(s) : 39 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background HOXB1 plays a major role in brainstem morphogenesis and could partly determine the cranial circumference in conjunction with HOXA1. In our sample, HOXA1 alleles significantly influence head growth rates both in autistic patients and in population controls. An initial report, suggesting that HOXB1 could confer autism vulnerability in interaction with HOXA1, was not confirmed by five small association studies. Methods Our sample includes 269 autistic individuals, belonging to 219 simplex and 28 multiplex families. A mutational analysis of the two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84 autistic patients by denaturing high performance liquid chromatography, followed by DNA sequencing. Identified rare variants were then searched by a restriction analysis in 236 autistic patients and 325-345 controls. Case-control and family-based association studies were performed on two common variants in 169 Italian patients versus 184 Italian controls and in 247 trios. Results We identified three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811 [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants, namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N). SNPs rs72338773 and rs12939811 were not associated with autism, using either a case-control (alleles, exact P=0.13) or a family-based design [transmission/disequilibrium test (TDT)x2=1.774, P=0.183]. The rare variants, all inherited from one of the parents, were present in two Italian and in two Caucasian-American families. Autistic probands in two families surprisingly inherited a distinct rare variant from each parent. The IVS1+63A allele was present in 3/690 control chromosomes, whereas rare alleles at rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control chromosomes, respectively. The INS-T309 allele influenced head size, but its effect appears more modest and shows no interaction with HOXA1 alleles. The INS-T309 allele is also associated with more severe stereotypic behaviours, according to ADI-R scores (N= 60 patients, P<0.01). Conclusions HOXB1 mutations do not represent a common cause of autism, nor do HOXB1 common variants play important roles in autism vulnerability. HOXB1 provides minor, albeit detectable contributions to head circumference in autistic patients, with HOXA1 displaying more prominent effects. HOXB1 variants may modulate the clinical phenotype, especially in the area of stereotypic behaviours. En ligne : http://dx.doi.org/10.1186/2040-2392-1-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=103 [article] Candidate gene study of HOXB1 in autism spectrum disorder [Texte imprimé et/ou numérique] / Lucia A. MUSCARELLA, Auteur ; Carmela BRAVACCIO, Auteur ; Cindy SCHNEIDER, Auteur ; Monica SACCANI, Auteur ; Carlo LENTI, Auteur ; Roberto MILITERNI, Auteur ; Grazia GIANA, Auteur ; Riccardo ALESSANDRELLI, Auteur ; Barbara MANZI, Auteur ; Roberto SACCO, Auteur ; Vito GUARNIERI, Auteur ; Raun D. MELMED, Auteur ; Paolo CURATOLO, Auteur ; Antonio M. PERSICO, Auteur ; Leonardo D'AGRUMA, Auteur . - 2010 . - 39 p. Langues : Anglais (eng) in Molecular Autism > (May 2010) . - 39 p. Index. décimale : PER Périodiques Résumé : Background HOXB1 plays a major role in brainstem morphogenesis and could partly determine the cranial circumference in conjunction with HOXA1. In our sample, HOXA1 alleles significantly influence head growth rates both in autistic patients and in population controls. An initial report, suggesting that HOXB1 could confer autism vulnerability in interaction with HOXA1, was not confirmed by five small association studies. Methods Our sample includes 269 autistic individuals, belonging to 219 simplex and 28 multiplex families. A mutational analysis of the two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84 autistic patients by denaturing high performance liquid chromatography, followed by DNA sequencing. Identified rare variants were then searched by a restriction analysis in 236 autistic patients and 325-345 controls. Case-control and family-based association studies were performed on two common variants in 169 Italian patients versus 184 Italian controls and in 247 trios. Results We identified three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811 [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants, namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N). SNPs rs72338773 and rs12939811 were not associated with autism, using either a case-control (alleles, exact P=0.13) or a family-based design [transmission/disequilibrium test (TDT)x2=1.774, P=0.183]. The rare variants, all inherited from one of the parents, were present in two Italian and in two Caucasian-American families. Autistic probands in two families surprisingly inherited a distinct rare variant from each parent. The IVS1+63A allele was present in 3/690 control chromosomes, whereas rare alleles at rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control chromosomes, respectively. The INS-T309 allele influenced head size, but its effect appears more modest and shows no interaction with HOXA1 alleles. The INS-T309 allele is also associated with more severe stereotypic behaviours, according to ADI-R scores (N= 60 patients, P<0.01). Conclusions HOXB1 mutations do not represent a common cause of autism, nor do HOXB1 common variants play important roles in autism vulnerability. HOXB1 provides minor, albeit detectable contributions to head circumference in autistic patients, with HOXA1 displaying more prominent effects. HOXB1 variants may modulate the clinical phenotype, especially in the area of stereotypic behaviours. En ligne : http://dx.doi.org/10.1186/2040-2392-1-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=103

A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder / Benjamin L. HANDEN in Journal of Autism and Developmental Disorders, 39-5 (May 2009)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 39-5 (May 2009) . - p.796-805 Titre : A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Benjamin L. HANDEN, Auteur ; Michael G. AMAN, Auteur ; Christopher J. MCDOUGLE, Auteur ; Raun D. MELMED, Auteur ; David L. BURNHAM, Auteur ; Jon B. BRUSS, Auteur ; David J. HANSEN, Auteur Année de publication : 2009 Article en page(s) : p.796-805 Langues : Anglais (eng) Mots-clés : Autism Gastrointestinal-symptoms Oral-human immunoglobulin Index. décimale : PER Périodiques Résumé : Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2–17 years) with autism and persistent GI symptoms. Endpoint analysis revealed no significant differences across treatment groups on a modified global improvement scale (validated in irritable bowel syndrome studies), number of daily bowel movements, days of constipation, or severity of problem behaviors. IGOH was well-tolerated; there were no serious adverse events. This study demonstrates the importance of conducting rigorous trials in children with autism and casts doubt on one GI mechanism presumed to exert etiological and/or symptomatic effects in this population. En ligne : http://dx.doi.org/10.1007/s10803-008-0687-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=733 [article] A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder [Texte imprimé et/ou numérique] / Benjamin L. HANDEN, Auteur ; Michael G. AMAN, Auteur ; Christopher J. MCDOUGLE, Auteur ; Raun D. MELMED, Auteur ; David L. BURNHAM, Auteur ; Jon B. BRUSS, Auteur ; David J. HANSEN, Auteur . - 2009 . - p.796-805. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 39-5 (May 2009) . - p.796-805 Mots-clés : Autism Gastrointestinal-symptoms Oral-human immunoglobulin Index. décimale : PER Périodiques Résumé : Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2–17 years) with autism and persistent GI symptoms. Endpoint analysis revealed no significant differences across treatment groups on a modified global improvement scale (validated in irritable bowel syndrome studies), number of daily bowel movements, days of constipation, or severity of problem behaviors. IGOH was well-tolerated; there were no serious adverse events. This study demonstrates the importance of conducting rigorous trials in children with autism and casts doubt on one GI mechanism presumed to exert etiological and/or symptomatic effects in this population. En ligne : http://dx.doi.org/10.1007/s10803-008-0687-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=733

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study / Craig ERICKSON in Journal of Autism and Developmental Disorders, 44-4 (April 2014)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 44-4 (April 2014) . - p.958-964 Titre : STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study Type de document : Texte imprimé et/ou numérique Auteurs : Craig ERICKSON, Auteur ; Jeremy M. VEENSTRA-VANDERWEELE, Auteur ; Raun D. MELMED, Auteur ; James T. MCCRACKEN, Auteur ; Lawrence D. GINSBERG, Auteur ; Linmarie SIKICH, Auteur ; Lawrence SCAHILL, Auteur ; Maryann CHERUBINI, Auteur ; Peter ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; Randall L. CARPENTER, Auteur ; Mark F. BEAR, Auteur ; Paul P. WANG, Auteur ; Bryan H. KING, Auteur Année de publication : 2014 Article en page(s) : p.958-964 Langues : Anglais (eng) Mots-clés : STX209  Arbaclofen  Gamma-aminobutyric acid (GABA)  Autism spectrum disorder  Clinical trial Index. décimale : PER Périodiques Résumé : STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ?17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted. En ligne : http://dx.doi.org/10.1007/s10803-013-1963-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228 [article] STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study [Texte imprimé et/ou numérique] / Craig ERICKSON, Auteur ; Jeremy M. VEENSTRA-VANDERWEELE, Auteur ; Raun D. MELMED, Auteur ; James T. MCCRACKEN, Auteur ; Lawrence D. GINSBERG, Auteur ; Linmarie SIKICH, Auteur ; Lawrence SCAHILL, Auteur ; Maryann CHERUBINI, Auteur ; Peter ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; Randall L. CARPENTER, Auteur ; Mark F. BEAR, Auteur ; Paul P. WANG, Auteur ; Bryan H. KING, Auteur . - 2014 . - p.958-964. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 44-4 (April 2014) . - p.958-964 Mots-clés : STX209  Arbaclofen  Gamma-aminobutyric acid (GABA)  Autism spectrum disorder  Clinical trial Index. décimale : PER Périodiques Résumé : STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ?17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted. En ligne : http://dx.doi.org/10.1007/s10803-013-1963-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228

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