Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms / Alina GUNA in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.18 Titre : Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms Type de document : texte imprimé Auteurs : Alina GUNA, Auteur ; Nancy J. BUTCHER, Auteur ; Anne S. BASSETT, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Mots-clés : Animal models  Dgcr8  DiGeorge syndrome  Homolog  Homology  Prodh  Slc25a1  Tbx1  Velocardiofacial syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common micro-deletion syndrome. The associated 22q11.2 deletion conveys the strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful in determining the role of some genes overlapped by the hemizygous 22q11.2 deletion in phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited in exploring these genotype-phenotype relationships. METHODS: We first developed a comprehensive map of the human 22q11.2 deletion region, delineating gene content, and brain expression. To identify putative orthologs, standard methods were used to interrogate the proteomes of the zebrafish (D. rerio), fruit fly (D. melanogaster), and worm (C. elegans), in addition to the mouse. Spatial locations of conserved homologues were mapped to examine syntenic relationships. We systematically cataloged available knockout and knockdown models of all conserved genes across these organisms, including a comprehensive review of associated phenotypes. RESULTS: There are 90 genes overlapped by the typical 2.5 Mb deletion 22q11.2 region. Of the 46 protein-coding genes, 41 (89.1 %) have documented expression in the human brain. Identified homologues in the zebrafish (n = 37, 80.4 %) were comparable to those in the mouse (n = 40, 86.9 %) and included some conserved gene cluster structures. There were 22 (47.8 %) putative homologues in the fruit fly and 17 (37.0 %) in the worm involving multiple chromosomes. Individual gene knockdown mutants were available for the simple model organisms, but not for mouse. Although phenotypic data were relatively limited for knockout and knockdown models of the 17 genes conserved across all species, there was some evidence for roles in neurodevelopmental phenotypes, including four of the six mitochondrial genes in the 22q11.2 deletion region. CONCLUSIONS: Simple model organisms represent a powerful but underutilized means of investigating the molecular mechanisms underlying the elevated risk for neurodevelopmental disorders in 22q11.2DS. This comparative multi-species study provides novel resources and support for the potential utility of non-mouse models in expression studies and high-throughput drug screening. The approach has implications for other recurrent copy number variations associated with neurodevelopmental phenotypes. En ligne : http://dx.doi.org/10.1186/s11689-015-9113-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 [article] Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms [texte imprimé] / Alina GUNA, Auteur ; Nancy J. BUTCHER, Auteur ; Anne S. BASSETT, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.18 Mots-clés : Animal models  Dgcr8  DiGeorge syndrome  Homolog  Homology  Prodh  Slc25a1  Tbx1  Velocardiofacial syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common micro-deletion syndrome. The associated 22q11.2 deletion conveys the strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful in determining the role of some genes overlapped by the hemizygous 22q11.2 deletion in phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited in exploring these genotype-phenotype relationships. METHODS: We first developed a comprehensive map of the human 22q11.2 deletion region, delineating gene content, and brain expression. To identify putative orthologs, standard methods were used to interrogate the proteomes of the zebrafish (D. rerio), fruit fly (D. melanogaster), and worm (C. elegans), in addition to the mouse. Spatial locations of conserved homologues were mapped to examine syntenic relationships. We systematically cataloged available knockout and knockdown models of all conserved genes across these organisms, including a comprehensive review of associated phenotypes. RESULTS: There are 90 genes overlapped by the typical 2.5 Mb deletion 22q11.2 region. Of the 46 protein-coding genes, 41 (89.1 %) have documented expression in the human brain. Identified homologues in the zebrafish (n = 37, 80.4 %) were comparable to those in the mouse (n = 40, 86.9 %) and included some conserved gene cluster structures. There were 22 (47.8 %) putative homologues in the fruit fly and 17 (37.0 %) in the worm involving multiple chromosomes. Individual gene knockdown mutants were available for the simple model organisms, but not for mouse. Although phenotypic data were relatively limited for knockout and knockdown models of the 17 genes conserved across all species, there was some evidence for roles in neurodevelopmental phenotypes, including four of the six mitochondrial genes in the 22q11.2 deletion region. CONCLUSIONS: Simple model organisms represent a powerful but underutilized means of investigating the molecular mechanisms underlying the elevated risk for neurodevelopmental disorders in 22q11.2DS. This comparative multi-species study provides novel resources and support for the potential utility of non-mouse models in expression studies and high-throughput drug screening. The approach has implications for other recurrent copy number variations associated with neurodevelopmental phenotypes. En ligne : http://dx.doi.org/10.1186/s11689-015-9113-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347

Research Review: Measuring life impact of youth mental health difficulties: scoping umbrella review of 80 instruments / Karolin R. KRAUSE in Journal of Child Psychology and Psychiatry, 67-8 (August 2026)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 67-8 (August 2026) . - p.1412-1441 Titre : Research Review: Measuring life impact of youth mental health difficulties: scoping umbrella review of 80 instruments Type de document : texte imprimé Auteurs : Karolin R. KRAUSE, Auteur ; Sophie CHUNG, Auteur ; Christiane KONSTANTOPOULOS, Auteur ; Terri RODAK, Auteur ; Ana CALDERÓN, Auteur ; Nichol Edwards SNAGG, Auteur ; Kristin CLEVERLEY, Auteur ; Nancy J. BUTCHER, Auteur ; Giovanni A. SALUM, Auteur ; Kathleen R. MERIKANGAS, Auteur ; Peter SZATMARI, Auteur Article en page(s) : p.1412-1441 Langues : Anglais (eng) Mots-clés : Outcome measures  functioning  quality of life  well-being  children  adolescents Index. décimale : PER Périodiques Résumé : Background Mental health symptoms affect children and youths' functioning, quality of life (QOL), and well-being in daily life. While this ?life impact? is a critical outcome, there is a lack of conceptual clarity and widely endorsed outcome measurement instruments (OMI) to support consistent assessment across studies. This scoping umbrella review sought to map OMIs that assess life impact through measures of functioning, QOL, or well-being. Specifically, our aims were to: identify life impact OMIs from existing reviews, compare OMI design characteristics, descriptively appraise essential aspects of development quality for selected OMIs, and assess how consistently reviews identified OMI target constructs. Methods We searched six databases for systematic, scoping, rapid, or narrative reviews of functioning, QOL, or well-being OMIs for 6-to-24-year-olds with primary mental health concerns. We separately retrieved original development/validation reports for each OMI and extracted information on the target construct and key design characteristics. For a subset of OMIs, we descriptively appraised essential features of OMI development quality. Results We identified 80 OMIs of functioning (n?=?35), QOL (n?=?33), and well-being (n?=?12). Two-thirds were developed for children and youth up to 18?years, but none targeted young adults aged 19?24. Functioning OMIs were frequently designed for multi-informant assessment; QOL and well-being OMIs were mainly self-reported. Most functioning OMIs were originally validated in populations with mental health difficulties, unlike OMIs of QOL and well-being. For over one quarter of OMIs, the target construct was misclassified in at least one review, with frequent conflation of QOL and well-being. Conclusions Mental health difficulties impact life across functioning, QOL, and well-being. Life impact is a core outcome to track in clinical research and practice. This review provides a roadmap to selecting OMIs of life impact in youth mental health based on OMI design characteristics. En ligne : https://doi.org/10.1111/jcpp.70134 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=592 [article] Research Review: Measuring life impact of youth mental health difficulties: scoping umbrella review of 80 instruments [texte imprimé] / Karolin R. KRAUSE, Auteur ; Sophie CHUNG, Auteur ; Christiane KONSTANTOPOULOS, Auteur ; Terri RODAK, Auteur ; Ana CALDERÓN, Auteur ; Nichol Edwards SNAGG, Auteur ; Kristin CLEVERLEY, Auteur ; Nancy J. BUTCHER, Auteur ; Giovanni A. SALUM, Auteur ; Kathleen R. MERIKANGAS, Auteur ; Peter SZATMARI, Auteur . - p.1412-1441. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 67-8 (August 2026) . - p.1412-1441 Mots-clés : Outcome measures  functioning  quality of life  well-being  children  adolescents Index. décimale : PER Périodiques Résumé : Background Mental health symptoms affect children and youths' functioning, quality of life (QOL), and well-being in daily life. While this ?life impact? is a critical outcome, there is a lack of conceptual clarity and widely endorsed outcome measurement instruments (OMI) to support consistent assessment across studies. This scoping umbrella review sought to map OMIs that assess life impact through measures of functioning, QOL, or well-being. Specifically, our aims were to: identify life impact OMIs from existing reviews, compare OMI design characteristics, descriptively appraise essential aspects of development quality for selected OMIs, and assess how consistently reviews identified OMI target constructs. Methods We searched six databases for systematic, scoping, rapid, or narrative reviews of functioning, QOL, or well-being OMIs for 6-to-24-year-olds with primary mental health concerns. We separately retrieved original development/validation reports for each OMI and extracted information on the target construct and key design characteristics. For a subset of OMIs, we descriptively appraised essential features of OMI development quality. Results We identified 80 OMIs of functioning (n?=?35), QOL (n?=?33), and well-being (n?=?12). Two-thirds were developed for children and youth up to 18?years, but none targeted young adults aged 19?24. Functioning OMIs were frequently designed for multi-informant assessment; QOL and well-being OMIs were mainly self-reported. Most functioning OMIs were originally validated in populations with mental health difficulties, unlike OMIs of QOL and well-being. For over one quarter of OMIs, the target construct was misclassified in at least one review, with frequent conflation of QOL and well-being. Conclusions Mental health difficulties impact life across functioning, QOL, and well-being. Life impact is a core outcome to track in clinical research and practice. This review provides a roadmap to selecting OMIs of life impact in youth mental health based on OMI design characteristics. En ligne : https://doi.org/10.1111/jcpp.70134 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=592

---

1 (1 - 2 / 2) Par page : 25 50 100 200