A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder / Megha SANTHOSH ; Emily NEUHAUS ; Catherine A.W. SULLIVAN ; Raphael A. BERNIER ; Susan Y. BOOKHEIMER ; Mirella DAPRETTO ; Daniel H. GESCHWIND ; Allison JACK ; James C. MCPARTLAND ; John D. VAN HORN ; Kevin A. PELPHREY ; Abha R. GUPTA ; Sara Jane WEBB ; THE A.C.E. GENDAAR NETWORK in Autism Research, 18-5 (May 2025)  

Public ISBD [article]  inAutism Research > 18-5 (May 2025) . - p.898-908 Titre : A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Megha SANTHOSH, Auteur ; Emily NEUHAUS, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Raphael A. BERNIER, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Daniel H. GESCHWIND, Auteur ; Allison JACK, Auteur ; James C. MCPARTLAND, Auteur ; John D. VAN HORN, Auteur ; Kevin A. PELPHREY, Auteur ; Abha R. GUPTA, Auteur ; Sara Jane WEBB, Auteur ; THE A.C.E. GENDAAR NETWORK, Auteur Article en page(s) : p.898-908 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  communication  language  SNP rs2710102  the polymorphism of CNTNAP2 Index. décimale : PER Périodiques Résumé : Abstract One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD. En ligne : https://doi.org/10.1002/aur.3193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558 [article] A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder [texte imprimé] / Megha SANTHOSH, Auteur ; Emily NEUHAUS, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Raphael A. BERNIER, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Daniel H. GESCHWIND, Auteur ; Allison JACK, Auteur ; James C. MCPARTLAND, Auteur ; John D. VAN HORN, Auteur ; Kevin A. PELPHREY, Auteur ; Abha R. GUPTA, Auteur ; Sara Jane WEBB, Auteur ; THE A.C.E. GENDAAR NETWORK, Auteur . - p.898-908. Langues : Anglais (eng) in Autism Research > 18-5 (May 2025) . - p.898-908 Mots-clés : Autism Spectrum Disorder  communication  language  SNP rs2710102  the polymorphism of CNTNAP2 Index. décimale : PER Périodiques Résumé : Abstract One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD. En ligne : https://doi.org/10.1002/aur.3193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558

Neurogenetic analysis of childhood disintegrative disorder / Abha R. GUPTA in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 19p. Titre : Neurogenetic analysis of childhood disintegrative disorder Type de document : texte imprimé Auteurs : Abha R. GUPTA, Auteur ; Alexander WESTPHAL, Auteur ; Daniel Y.J. YANG, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Jeffrey EILBOTT, Auteur ; Samir ZAIDI, Auteur ; Avery VOOS, Auteur ; Brent C. VANDER WYK, Auteur ; Pamela VENTOLA, Auteur ; Zainulabedin WAQAR, Auteur ; Thomas V. FERNANDEZ, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; Michael F. WALKER, Auteur ; M. CHOI, Auteur ; Andrea SCHNEIDER, Auteur ; Tammy HEDDERLY, Auteur ; Gillian BAIRD, Auteur ; Hannah FRIEDMAN, Auteur ; Cara CORDEAUX, Auteur ; Alexandra RISTOW, Auteur ; Frederick SHIC, Auteur ; Fred R. VOLKMAR, Auteur ; Kevin A. PELPHREY, Auteur Article en page(s) : 19p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Childhood disintegrative disorder (CDD)  Eye tracking  Functional magnetic resonance imaging (fMRI)  Genetics  Intellectual disability (ID)  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. METHODS: We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. RESULTS: We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. CONCLUSIONS: Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level. En ligne : http://dx.doi.org/10.1186/s13229-017-0133-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Neurogenetic analysis of childhood disintegrative disorder [texte imprimé] / Abha R. GUPTA, Auteur ; Alexander WESTPHAL, Auteur ; Daniel Y.J. YANG, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Jeffrey EILBOTT, Auteur ; Samir ZAIDI, Auteur ; Avery VOOS, Auteur ; Brent C. VANDER WYK, Auteur ; Pamela VENTOLA, Auteur ; Zainulabedin WAQAR, Auteur ; Thomas V. FERNANDEZ, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; Michael F. WALKER, Auteur ; M. CHOI, Auteur ; Andrea SCHNEIDER, Auteur ; Tammy HEDDERLY, Auteur ; Gillian BAIRD, Auteur ; Hannah FRIEDMAN, Auteur ; Cara CORDEAUX, Auteur ; Alexandra RISTOW, Auteur ; Frederick SHIC, Auteur ; Fred R. VOLKMAR, Auteur ; Kevin A. PELPHREY, Auteur . - 19p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 19p. Mots-clés : Autism spectrum disorder (ASD)  Childhood disintegrative disorder (CDD)  Eye tracking  Functional magnetic resonance imaging (fMRI)  Genetics  Intellectual disability (ID)  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. METHODS: We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. RESULTS: We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. CONCLUSIONS: Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level. En ligne : http://dx.doi.org/10.1186/s13229-017-0133-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder / Meredith GOODRICH in Autism Research, 12-2 (February 2019)  

Public ISBD [article]  inAutism Research > 12-2 (February 2019) . - p.200-211 Titre : PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Meredith GOODRICH, Auteur ; Anna Chelsea ARMOUR, Auteur ; Karuna PANCHAPAKESAN, Auteur ; Xiaozhen YOU, Auteur ; Joseph DEVANEY, Auteur ; Susan KNOBLACH, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Maria Jesus HERRERO, Auteur ; Abha R. GUPTA, Auteur ; Chandan J. VAIDYA, Auteur ; Lauren KENWORTHY, Auteur ; Joshua G. CORBIN, Auteur Article en page(s) : p.200-211 Langues : Anglais (eng) Mots-clés : Pac1r  amygdala  autism  genetic modifier  neuroimaging Index. décimale : PER Périodiques Résumé : Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2019, 12: 200-211 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD. En ligne : http://dx.doi.org/10.1002/aur.2051 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383 [article] PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder [texte imprimé] / Meredith GOODRICH, Auteur ; Anna Chelsea ARMOUR, Auteur ; Karuna PANCHAPAKESAN, Auteur ; Xiaozhen YOU, Auteur ; Joseph DEVANEY, Auteur ; Susan KNOBLACH, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Maria Jesus HERRERO, Auteur ; Abha R. GUPTA, Auteur ; Chandan J. VAIDYA, Auteur ; Lauren KENWORTHY, Auteur ; Joshua G. CORBIN, Auteur . - p.200-211. Langues : Anglais (eng) in Autism Research > 12-2 (February 2019) . - p.200-211 Mots-clés : Pac1r  amygdala  autism  genetic modifier  neuroimaging Index. décimale : PER Périodiques Résumé : Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2019, 12: 200-211 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD. En ligne : http://dx.doi.org/10.1002/aur.2051 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383

---

1 (1 - 3 / 3) Par page : 25 50 100 200