Decreased tryptophan metabolism in patients with autism spectrum disorders / Luigi BOCCUTO in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 10 p. Titre : Decreased tryptophan metabolism in patients with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur Année de publication : 2013 Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarker  Tryptophan  Metabolism  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Decreased tryptophan metabolism in patients with autism spectrum disorders [Texte imprimé et/ou numérique] / Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur . - 2013 . - 10 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 10 p. Mots-clés : Autism  Biomarker  Tryptophan  Metabolism  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder / Rini PAULY in Research in Autism Spectrum Disorders, 85 (July 2021)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 85 (July 2021) . - 101790 Titre : Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Rini PAULY, Auteur ; Lauren CASCIO, Auteur ; Sujata SRIKANTH, Auteur ; Kelly JONES, Auteur ; Skylar SORROW, Auteur ; Rossana CUBILLAN, Auteur ; Chin-Fu CHEN, Auteur ; Cindy SKINNER, Auteur ; Kevin CHAMPAIGNE, Auteur ; Roger E. STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur Article en page(s) : 101790 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Tryptophan  Metabolism  Diagnostic test  Screening test Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition with a tremendous impact on society and families. The biological basis of ASD has yet to be completely understood and there are no laboratory tests for this condition. Phenotype Mammalian Microarrays (PM-Ms) can distinguish patients with ASD from typically developing (TD) individuals by differential utilization of the amino acid tryptophan. By assessing several parameters of the assay utilizing customized tryptophan-containing PM-M plates, we improved the discrimination of the test, optimized test parameters, and minimized background noise by normalization while controlling for false discoveries. This improved platform can provide the first cell-based metabolic test to validate the clinical diagnosis of ASD and possibly identify individuals at risk even before the occurrence of neuro-behavioral symptoms. En ligne : https://doi.org/10.1016/j.rasd.2021.101790 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458 [article] Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder [Texte imprimé et/ou numérique] / Rini PAULY, Auteur ; Lauren CASCIO, Auteur ; Sujata SRIKANTH, Auteur ; Kelly JONES, Auteur ; Skylar SORROW, Auteur ; Rossana CUBILLAN, Auteur ; Chin-Fu CHEN, Auteur ; Cindy SKINNER, Auteur ; Kevin CHAMPAIGNE, Auteur ; Roger E. STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur . - 101790. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 85 (July 2021) . - 101790 Mots-clés : Autism spectrum disorder (ASD)  Tryptophan  Metabolism  Diagnostic test  Screening test Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition with a tremendous impact on society and families. The biological basis of ASD has yet to be completely understood and there are no laboratory tests for this condition. Phenotype Mammalian Microarrays (PM-Ms) can distinguish patients with ASD from typically developing (TD) individuals by differential utilization of the amino acid tryptophan. By assessing several parameters of the assay utilizing customized tryptophan-containing PM-M plates, we improved the discrimination of the test, optimized test parameters, and minimized background noise by normalization while controlling for false discoveries. This improved platform can provide the first cell-based metabolic test to validate the clinical diagnosis of ASD and possibly identify individuals at risk even before the occurrence of neuro-behavioral symptoms. En ligne : https://doi.org/10.1016/j.rasd.2021.101790 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458

Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder / Pamela B. JACKSON in Autism Research, 2-4 (August 2009)  

Public ISBD [article]  inAutism Research > 2-4 (August 2009) . - p.232-236 Titre : Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder Type de document : Texte imprimé et/ou numérique Auteurs : Pamela B. JACKSON, Auteur ; Luigi BOCCUTO, Auteur ; Cindy SKINNER, Auteur ; Julianne S. COLLINS, Auteur ; Giovanni NERI, Auteur ; Fiorella GURRIERI, Auteur ; Charles E. SCHWARTZ, Auteur Année de publication : 2009 Article en page(s) : p.232-236 Langues : Anglais (eng) Mots-clés : autism autistic-disorder MET PDD PDD-NOS Index. décimale : PER Périodiques Résumé : Previous studies in three independent cohorts have shown that the rs1858830 C allele variant in the promoter region of the MET gene on chromosome 7q31 is associated with autism. Another study has found correlations between other alterations in the MET gene and autism in two unrelated cohorts. This study screened two cohorts, an Autistic Disorder cohort from South Carolina and a Pervasive Developmental Disorder (PDD) cohort from Italy, for the presence of the C allele variant in rs1858830. A significant increase in the C allele variant frequency was found in the South Carolina Autistic Disorder patients as compared to South Carolina Controls (2=5.8, df=1, P=0.02). In the South Carolina cohort, a significant association with Autistic Disorder was found when comparing the CC and CG genotypes to the GG genotype (odds ratio (OR)=1.64; 95% confidence interval (CI)=1.12-2.40; 2=6.5, df=1, P=0.01) in cases and controls. In the Italian cohort, no significant association with PDD was found when comparing the CC or CG genotype to the GG genotype (OR=1.20; 95% CI=0.56-2.56; 2=0.2, df=1, P=0.64). This study is the third independent study to find the rs1858830 C variant in the MET gene promoter to be associated with autism. En ligne : http://dx.doi.org/10.1002/aur.87 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=938 [article] Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder [Texte imprimé et/ou numérique] / Pamela B. JACKSON, Auteur ; Luigi BOCCUTO, Auteur ; Cindy SKINNER, Auteur ; Julianne S. COLLINS, Auteur ; Giovanni NERI, Auteur ; Fiorella GURRIERI, Auteur ; Charles E. SCHWARTZ, Auteur . - 2009 . - p.232-236. Langues : Anglais (eng) in Autism Research > 2-4 (August 2009) . - p.232-236 Mots-clés : autism autistic-disorder MET PDD PDD-NOS Index. décimale : PER Périodiques Résumé : Previous studies in three independent cohorts have shown that the rs1858830 C allele variant in the promoter region of the MET gene on chromosome 7q31 is associated with autism. Another study has found correlations between other alterations in the MET gene and autism in two unrelated cohorts. This study screened two cohorts, an Autistic Disorder cohort from South Carolina and a Pervasive Developmental Disorder (PDD) cohort from Italy, for the presence of the C allele variant in rs1858830. A significant increase in the C allele variant frequency was found in the South Carolina Autistic Disorder patients as compared to South Carolina Controls (2=5.8, df=1, P=0.02). In the South Carolina cohort, a significant association with Autistic Disorder was found when comparing the CC and CG genotypes to the GG genotype (odds ratio (OR)=1.64; 95% confidence interval (CI)=1.12-2.40; 2=6.5, df=1, P=0.01) in cases and controls. In the Italian cohort, no significant association with PDD was found when comparing the CC or CG genotype to the GG genotype (OR=1.20; 95% CI=0.56-2.56; 2=0.2, df=1, P=0.64). This study is the third independent study to find the rs1858830 C variant in the MET gene promoter to be associated with autism. En ligne : http://dx.doi.org/10.1002/aur.87 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=938

Genetics of X-Linked Intellectual Disability / Charles E. SCHWARTZ  

Public ISBD in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Titre : Genetics of X-Linked Intellectual Disability Type de document : Texte imprimé et/ou numérique Auteurs : Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur Année de publication : 2016 Importance : p.25-41 Langues : Anglais (eng) Mots-clés : Disease mechanisms  Nonsyndromal XLID  Syndromal XLID  X-linked intellectual disability Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Intellectual disability (ID) represents a heterogeneous disorder affecting the development, function, and/or structure of the central nervous system. ID affects about 2–3% of the general population, with a male excess estimated around 30%. Genetic defects on the X chromosome are supposed to have a major role in this gender bias. X-linked intellectual disability (XLID) can be grouped into two categories, syndromal and nonsyndromal, although some genes can be responsible for both forms. In the past 2 decades, important progress has been made in identifying new causative genes and understanding the disease mechanisms underlying over 100 XLID conditions. Most known genes involve one of the following functional groups: presynaptic vesicle cycling and transport, cytoskeletal dynamics, cell adhesion and transsynaptic signaling, and translational regulation. Expanding knowledge of XLID also allows researchers to design new therapeutic approaches. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00003-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Genetics of X-Linked Intellectual Disability [Texte imprimé et/ou numérique] / Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur . - 2016 . - p.25-41. Langues : Anglais (eng) Mots-clés : Disease mechanisms  Nonsyndromal XLID  Syndromal XLID  X-linked intellectual disability Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Intellectual disability (ID) represents a heterogeneous disorder affecting the development, function, and/or structure of the central nervous system. ID affects about 2–3% of the general population, with a male excess estimated around 30%. Genetic defects on the X chromosome are supposed to have a major role in this gender bias. X-linked intellectual disability (XLID) can be grouped into two categories, syndromal and nonsyndromal, although some genes can be responsible for both forms. In the past 2 decades, important progress has been made in identifying new causative genes and understanding the disease mechanisms underlying over 100 XLID conditions. Most known genes involve one of the following functional groups: presynaptic vesicle cycling and transport, cytoskeletal dynamics, cell adhesion and transsynaptic signaling, and translational regulation. Expanding knowledge of XLID also allows researchers to design new therapeutic approaches. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00003-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

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Phelan-McDermid Syndrome: Clinical Aspects / Katy PHELAN  

Public ISBD in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Titre : Phelan-McDermid Syndrome: Clinical Aspects Type de document : Texte imprimé et/ou numérique Auteurs : Katy PHELAN, Auteur ; Luigi BOCCUTO, Auteur ; Sara SARASUA, Auteur Année de publication : 2016 Importance : p.347-364 Langues : Anglais (eng) Mots-clés : 22q13 deletion  Absent speech  Autism  Dysplastic toenails  Hypotonia  Intellectual impairment  Phelan–McDermid  SHANK3  Speech delay Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Phelan–McDermid syndrome (PMS), also known as the 22q13 deletion syndrome, is a genetic condition characterized by neonatal hypotonia, developmental delay, absent or impaired speech, and minor dysmorphic features. PMS typically results from a deletion of the distal long arm of chromosome 22, with the size of the deleted segment ranging from less than 100 kb to greater than 9 MB. The loss of 22q13 may result from a terminal deletion, an interstitial deletion, an unbalanced translocation, formation of a ring chromosome, or other types of structural chromosome aberrations. In most cases, the deletion results in haploinsufficiency for the SHANK3 gene which codes for a scaffolding protein in the postsynaptic density of excitatory neurons. Mutation or disruption of the SHANK3 gene may also result in PMS. The diagnosis of PMS relies on laboratory confirmation by molecular cytogenetic or molecular genetic methods. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00021-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Phelan-McDermid Syndrome: Clinical Aspects [Texte imprimé et/ou numérique] / Katy PHELAN, Auteur ; Luigi BOCCUTO, Auteur ; Sara SARASUA, Auteur . - 2016 . - p.347-364. Langues : Anglais (eng) Mots-clés : 22q13 deletion  Absent speech  Autism  Dysplastic toenails  Hypotonia  Intellectual impairment  Phelan–McDermid  SHANK3  Speech delay Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Phelan–McDermid syndrome (PMS), also known as the 22q13 deletion syndrome, is a genetic condition characterized by neonatal hypotonia, developmental delay, absent or impaired speech, and minor dysmorphic features. PMS typically results from a deletion of the distal long arm of chromosome 22, with the size of the deleted segment ranging from less than 100 kb to greater than 9 MB. The loss of 22q13 may result from a terminal deletion, an interstitial deletion, an unbalanced translocation, formation of a ring chromosome, or other types of structural chromosome aberrations. In most cases, the deletion results in haploinsufficiency for the SHANK3 gene which codes for a scaffolding protein in the postsynaptic density of excitatory neurons. Mutation or disruption of the SHANK3 gene may also result in PMS. The diagnosis of PMS relies on laboratory confirmation by molecular cytogenetic or molecular genetic methods. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00021-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

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