AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission / C. M. YRIGOLLEN in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.24 Titre : AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission Type de document : Texte imprimé et/ou numérique Auteurs : C. M. YRIGOLLEN, Auteur ; L. MARTORELL, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; M. NAUDO, Auteur ; J. GENOVES, Auteur ; A. MURGIA, Auteur ; R. POLLI, Auteur ; L. ZHOU, Auteur ; D. BARBOUTH, Auteur ; A. RUPCHOCK, Auteur ; B. FINUCANE, Auteur ; G. J. LATHAM, Auteur ; A. HADD, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; F. TASSONE, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Mots-clés : AGG interruptions  Fmr1  full mutation  gray/intermediate allele  premutation  risk of expansion Index. décimale : PER Périodiques Résumé : BACKGROUND: The presence of AGG interruptions in the CGG repeat locus of the fragile X mental retardation 1 (FMR1) gene decreases the instability of the allele during transmission from parent to child, and decreases the risk of expansion of a premutation allele to a full mutation allele (the predominant cause of fragile X syndrome) during maternal transmission. METHODS: To strengthen recent findings on the utility of AGG interruptions in predicting instability or expansion to a full mutation of FMR1 CGG repeat alleles, we assessed the outcomes of 108 intermediate (also named gray zone) and 710 premutation alleles that were transmitted from parent to child, and collected from four international clinical sites. We have used the results to revise our initial model that predicted the risk of a maternal premutation allele expanding to a full mutation during transmission and to test the effect of AGG interruptions on the magnitude of expanded allele instability of intermediate or premutation alleles that did not expand to a full mutation. RESULTS: Consistent with previous studies, the number of AGG triplets that interrupts the CGG repeat locus was found to influence the risk of allele instability, including expansion to a full mutation. The total length of the CGG repeat allele remains the best predictor of instability or expansion to a full mutation, but the number of AGG interruptions and, to a much lesser degree, maternal age are also factors when considering the risk of transmission of the premutation allele to a full mutation. CONCLUSIONS: Our findings demonstrate that a model with total CGG length, number of AGG interruptions, and maternal age is recommended for calculating the risk of expansion to a full mutation during maternal transmission. Taken together, the results of this study provide relevant information for the genetic counseling of female premutation carriers, and improve the current predictive models which calculate risk of expansion to a full mutation using only total CGG repeat length. En ligne : http://dx.doi.org/10.1186/1866-1955-6-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission [Texte imprimé et/ou numérique] / C. M. YRIGOLLEN, Auteur ; L. MARTORELL, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; M. NAUDO, Auteur ; J. GENOVES, Auteur ; A. MURGIA, Auteur ; R. POLLI, Auteur ; L. ZHOU, Auteur ; D. BARBOUTH, Auteur ; A. RUPCHOCK, Auteur ; B. FINUCANE, Auteur ; G. J. LATHAM, Auteur ; A. HADD, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; F. TASSONE, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.24 Mots-clés : AGG interruptions  Fmr1  full mutation  gray/intermediate allele  premutation  risk of expansion Index. décimale : PER Périodiques Résumé : BACKGROUND: The presence of AGG interruptions in the CGG repeat locus of the fragile X mental retardation 1 (FMR1) gene decreases the instability of the allele during transmission from parent to child, and decreases the risk of expansion of a premutation allele to a full mutation allele (the predominant cause of fragile X syndrome) during maternal transmission. METHODS: To strengthen recent findings on the utility of AGG interruptions in predicting instability or expansion to a full mutation of FMR1 CGG repeat alleles, we assessed the outcomes of 108 intermediate (also named gray zone) and 710 premutation alleles that were transmitted from parent to child, and collected from four international clinical sites. We have used the results to revise our initial model that predicted the risk of a maternal premutation allele expanding to a full mutation during transmission and to test the effect of AGG interruptions on the magnitude of expanded allele instability of intermediate or premutation alleles that did not expand to a full mutation. RESULTS: Consistent with previous studies, the number of AGG triplets that interrupts the CGG repeat locus was found to influence the risk of allele instability, including expansion to a full mutation. The total length of the CGG repeat allele remains the best predictor of instability or expansion to a full mutation, but the number of AGG interruptions and, to a much lesser degree, maternal age are also factors when considering the risk of transmission of the premutation allele to a full mutation. CONCLUSIONS: Our findings demonstrate that a model with total CGG length, number of AGG interruptions, and maternal age is recommended for calculating the risk of expansion to a full mutation during maternal transmission. Taken together, the results of this study provide relevant information for the genetic counseling of female premutation carriers, and improve the current predictive models which calculate risk of expansion to a full mutation using only total CGG repeat length. En ligne : http://dx.doi.org/10.1186/1866-1955-6-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment / Yihui ZHU in Autism Research, 14-1 (January 2021)  

Public ISBD [article]  inAutism Research > 14-1 (January 2021) . - p.11-28 Titre : Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment Type de document : Texte imprimé et/ou numérique Auteurs : Yihui ZHU, Auteur ; Charles E. MORDAUNT, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; Marie A. CAUDILL, Auteur ; Olga V. MALYSHEVA, Auteur ; Joshua W. MILLER, Auteur ; Ralph GREEN, Auteur ; S. Jill JAMES, Auteur ; Stepan B. MELNYK, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Rebecca J. SCHMIDT, Auteur ; Janine M. LASALLE, Auteur Article en page(s) : p.11-28 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  maternal blood  neurodevelopment  nutrition  one-carbon metabolites  prenatal  transcriptome Index. décimale : PER Périodiques Résumé : The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients. En ligne : http://dx.doi.org/10.1002/aur.2428 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441 [article] Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment [Texte imprimé et/ou numérique] / Yihui ZHU, Auteur ; Charles E. MORDAUNT, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; Marie A. CAUDILL, Auteur ; Olga V. MALYSHEVA, Auteur ; Joshua W. MILLER, Auteur ; Ralph GREEN, Auteur ; S. Jill JAMES, Auteur ; Stepan B. MELNYK, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Rebecca J. SCHMIDT, Auteur ; Janine M. LASALLE, Auteur . - p.11-28. Langues : Anglais (eng) in Autism Research > 14-1 (January 2021) . - p.11-28 Mots-clés : autism spectrum disorder  maternal blood  neurodevelopment  nutrition  one-carbon metabolites  prenatal  transcriptome Index. décimale : PER Périodiques Résumé : The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients. En ligne : http://dx.doi.org/10.1002/aur.2428 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441

Identification of Expanded Alleles of the FMR1 Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study / Flora TASSONE in Journal of Autism and Developmental Disorders, 43-3 (March 2013)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 43-3 (March 2013) . - p.530-539 Titre : Identification of Expanded Alleles of the FMR1 Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study Type de document : Texte imprimé et/ou numérique Auteurs : Flora TASSONE, Auteur ; Nimrah S. CHOUDHARY, Auteur ; Federica TASSONE, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; David J. HANSEN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Isaac N. PESSAH, Auteur Article en page(s) : p.530-539 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental delay  Fragile X  Premutation  Screening  CGG Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a neuro-developmental disorder characterized by intellectual disabilities and autism spectrum disorders (ASD). Expansion of a CGG trinucleotide repeat (200 repeats) in the 5?UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies for FXS, among individuals with ID from different ethnic populations, have indicated that the prevalence of the syndrome varies between 0.5 and 16 %. Because the high co-morbidity with autism, we have conducted a screening study of the cohort from CHARGE, a large-scale, population-based, case control study. We have identified six subjects carrying an expanded allele, which emphasize the importance of screening for FXS in a population with intellectual disabilities and ASD. En ligne : http://dx.doi.org/10.1007/s10803-012-1580-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=192 [article] Identification of Expanded Alleles of the FMR1 Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study [Texte imprimé et/ou numérique] / Flora TASSONE, Auteur ; Nimrah S. CHOUDHARY, Auteur ; Federica TASSONE, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; David J. HANSEN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Isaac N. PESSAH, Auteur . - p.530-539. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 43-3 (March 2013) . - p.530-539 Mots-clés : Autism spectrum disorder  Developmental delay  Fragile X  Premutation  Screening  CGG Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a neuro-developmental disorder characterized by intellectual disabilities and autism spectrum disorders (ASD). Expansion of a CGG trinucleotide repeat (200 repeats) in the 5?UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies for FXS, among individuals with ID from different ethnic populations, have indicated that the prevalence of the syndrome varies between 0.5 and 16 %. Because the high co-morbidity with autism, we have conducted a screening study of the cohort from CHARGE, a large-scale, population-based, case control study. We have identified six subjects carrying an expanded allele, which emphasize the importance of screening for FXS in a population with intellectual disabilities and ASD. En ligne : http://dx.doi.org/10.1007/s10803-012-1580-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=192

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