03 septembre 2017

L'efficacité de la thérapie de groupe aquatique pour améliorer la sécurité aquatique et les interactions sociales chez les enfants avec un diagnostic de "trouble du spectre de l'autisme": un programme pilote

Traduction: G.M.

J Autism Dev Disord. 2017 Sep 1. doi: 10.1007/s10803-017-3264-4.

The Effectiveness of Aquatic Group Therapy for Improving Water Safety and Social Interactions in Children with Autism Spectrum Disorder: A Pilot Program

Author information

1
Children's Services Center, Casa Colina Hospital and Centers for Healthcare, 255 E. Bonita Ave., P.O. Box 6001, Pomona, CA, 91769, USA. malaniz@casacolina.org.
2
Children's Services Center, Casa Colina Hospital and Centers for Healthcare, 255 E. Bonita Ave., P.O. Box 6001, Pomona, CA, 91769, USA.
3
Casa Colina's Research Institute, Pomona, CA, USA.
4
Curative New Berlin Therapies, New Berlin, WI, USA.
5
Children's Services Center, University of Southern California, Los Angeles, CA, USA.

Abstract

La noyade est la principale cause de décès accidentel chez les enfants avec un diagnostic de "trouble du spectre de l'autisme" (TSA). Peu d'études ont examiné l'efficacité des cours de natation pour améliorer les compétences en matière de sécurité aquatique chez les enfants avec "TSA modéré à sévère". Cette étude examine la faisabilité et l'efficacité d'un programme de thérapie aquatique sur la sécurité aquatique et sur les compétences sociales chez les enfants "avec un TSA léger à sévère (n = 7). Les compétences en sécurité aquatique ont été évaluées à l'aide de la Liste de vérification des compétences aquatiques et les compétences sociales ont été mesurées à l'aide de l'Échelle d'amélioration des compétences sociales. Nous fournissons des preuves préliminaires que les enfants avec un diagnostic de TSA peuvent améliorer les compétences en matière de sécurité aquatique (p = 0,0002), ce qui est important pour la prévention de la noyade après seulement 8 heures d'intervention. Cependant, les compétences sociales n'ont pas répondu à l'intervention (p = 0,6409).
 Drowning is the number one cause of accidental death in children with Autism Spectrum Disorder (ASD). Few studies have examined the effectiveness of swim instruction for improving water safety skills in children with moderate to severe ASD. This study examines the feasibility and effectiveness of an aquatic therapy program on water safety and social skills in children with mild to severe ASD (n = 7). Water safety skills were evaluated using the Aquatics Skills Checklist and social skills were measured using the Social Skills Improvement Scale. We provide preliminary evidence that children with ASD can improve water safety skills (p = 0.0002), which are important for drowning prevention after only 8 h of intervention. However, social skills did not respond to intervention (p = 0.6409).

PMID:28864911
DOI: 10.1007/s10803-017-3264-4

L'intensité perçue des présentation émotionnelles à partir de points lumineux est réduite chez les sujets avec un diagnostic de TSA

Aperçu: G.M.
La présente étude a exploré les altérations liées aux TSA dans la perception des émotions exprimées par les mouvements du corps. 16 participants avec un diagnostic de TSA et 16 contrôles sans TSA ont observé des scènes vidéo d'interactions humaines véhiculées par des écrans à points lumineux. 
Les résultats ont montré que les participants sans TSA ont évalué les interactions émotionnelles présentant une émotivité positive comme étant plus intenses et plus confiant quant à leur évaluation  que les sujets avec TSA . Les résultats confirment l'idée que les patients avec un diagnostic de TSA ont une perception altérée des émotions. Cela étend la recherche sur les caractéristiques subjectives (intensité, confiance) de la perception de l'émotion au domaine des mouvements du corps émotionnel et de la cinématique.

J Autism Dev Disord. 2017 Sep 1. doi: 10.1007/s10803-017-3286-y.

Perceived Intensity of Emotional Point-Light Displays is Reduced in Subjects with ASD

Author information

1
Institute for Sports Science, Justus Liebig University Giessen, Kugelberg 62, 35394, Giessen, Germany. britta.krueger@sport.uni-giessen.de.
2
Bender Institute of Neuroimaging, Justus Liebig University Giessen, Giessen, Germany. britta.krueger@sport.uni-giessen.de.
3
Cognitive Neuroscience Group, Center for Psychiatry and Psychotherapy, Justus Liebig University, Giessen, Germany.
4
Institute for Sports Science, Justus Liebig University Giessen, Kugelberg 62, 35394, Giessen, Germany.
5
Bender Institute of Neuroimaging, Justus Liebig University Giessen, Giessen, Germany.
6
Institute of Psychology, University of Hildesheim, Hildesheim, Germany.
7
Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
8
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
9
Institute for Sports Science, University of Munster, Munster, Germany.

Abstract

One major characteristic of autism spectrum disorder (ASD) is problems with social interaction and communication. The present study explored ASD-related alterations in perceiving emotions expressed via body movements. 16 participants with ASD and 16 healthy controls observed video scenes of human interactions conveyed by point-light displays. They rated the valence of the depicted emotions in terms of their intensity and judged their confidence in their ratings. Results showed that healthy participants rated emotional interactions displaying positive emotionality as being more intense and were more confident about their ratings than ASD subjects. Results support the idea that patients with ASD have an altered perception of emotions. This extends research on subjective features (intensity, confidence) of emotion perception to the domain of emotional body movements and kinematics.
PMID:28864932
DOI:10.1007/s10803-017-3286-y

Aperçu de la recherche sur l'oxycologie humaine

Aperçu: G.M.
À ce jour, la recherche a principalement tenté d'établir des effets fonctionnels en mesurant des concentrations endogènes altérées, en observant les effets de l'administration exogène et en étudiant les effets des polymorphismes et des modifications épigénétiques du gène du récepteur de l'ocytocine.
Les chercheurs résument quelques-uns des principaux résultats sur les effets comportementaux et neurologiques qui ont été signalés chez des sujets sains dans le contexte de la cognition sociale qui ont encouragé l'ocytocine à représenter une cible thérapeutique prometteuse. Ils ont aussi identifié un certain nombre de domaines clés dans lesquels il existe un besoin d'informations supplémentaires sur les stratégies de dosage optimales et les interactions avec d'autres systèmes de peptides et d'émetteurs. Enfin, ils ont résumé les résultats thérapeutiques de l'administration d'oxytocine intranasale dans l'autisme et la schizophrénie. 
Les résultats cliniques, bien que variés, offrent une cause d'optimisme croissante sur le fait que le ciblage du système d'ocytocine peut constituer une approche thérapeutique réussie pour le dysfonctionnement social. 
 

Curr Top Behav Neurosci. 2017 Sep 2. doi: 10.1007/7854_2017_19.

Overview of Human Oxytocin Research

Author information

1
Key Laboratory for Neuroinformation, School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China. k.kendrick.uestc@gmail.com.
2
Key Laboratory for Neuroinformation, School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China. adam.guastella@sydney.edu.au.
3
Brain and Mind Center, University of Sydney, Sydney, NSW, Australia. adam.guastella@sydney.edu.au.
4
Key Laboratory for Neuroinformation, School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China. ben_becker@gmx.de.

Abstract

Social dysfunction is a core symptom of many psychiatric disorders and current medications have little or no remedial effects on this. Following on from extensive studies on animal models demonstrating that the neuropeptide oxytocin plays an important role in social recognition and bonding, human-based research has explored its therapeutic potential for social dysfunction in psychiatric disorders. Here we outline the historical background of this human-based research and some of the current methodological challenges it is facing. To date, research has primarily attempted to establish functional effects through measuring altered endogenous concentrations, observing effects of exogenous administration and by investigating the effects of polymorphisms and epigenetic modifications of the oxytocin receptor gene. We summarize some of the key findings on behavioral and neural effects that have been reported in healthy subjects in the context of social cognition which have provided encouragement that oxytocin could represent a promising therapeutic target. At the same time, we have identified a number of key areas where we urgently need further information about optimal dosing strategies and interactions with other peptide and transmitter systems. Finally, we have summarized current translational findings, particularly in the context of therapeutic outcomes of intranasal oxytocin administration in autism and schizophrenia. These clinical findings while somewhat varied in outcome do offer increasing cause for optimism that targeting the oxytocin system may provide a successful therapeutic approach for social dysfunction. However, future research needs to focus on the most effective treatment strategy and which types of individuals are likely to benefit most.
PMID:28864976
DOI:10.1007/7854_2017_19

Ocytocine et modèles animaux pour le "trouble du spectre de l'autisme"

Aperçu: G.M.
Au cours de la dernière décennie, il y a eu un intérêt important dans l'utilisation de l'ocytocine pour traiter les déficits de comportement social dans le TSA. Cependant, on a accordé peu d'attention pour savoir si le système d'ocytocine est perturbé dans des sous-groupes de personnes avec un diagnostic de TSA et si ces personnes sont susceptibles de bénéficier davantage d'un traitement par l'ocytocine. 
Cela peut être dû en partie à l'énorme hétérogénéité des TSA et au manque de méthodes pour soigneusement sonder le système OXT chez les sujets humains. Les modèles animaux pour le TSA sont des outils précieux pour clarifier l'implication du système d'ocytocine dans le TSA.
 

Curr Top Behav Neurosci. 2017 Sep 2. doi: 10.1007/7854_2017_15.

Oxytocin and Animal Models for Autism Spectrum Disorder

Author information

1
Sagol Department of Neurobiology, The University of Haifa, Haifa, Israel.
2
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Hala.Harony-Nicolas@mssm.edu.
3
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Hala.Harony-Nicolas@mssm.edu.

Abstract

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions characterized by deficits in social communication and by repetitive and stereotypic patterns of behaviors, with no pharmacological treatments available to treat these core symptoms. Oxytocin is a neuropeptide that powerfully regulates mammalian social behavior and has been shown to exert pro-social effects when administered intranasally to healthy human subjects. In the last decade, there has been a significant interest in using oxytocin to treat social behavior deficits in ASD. However, little attention has been paid to whether the oxytocin system is perturbed in subgroups of individuals with ASD and whether these individuals are likely to benefit more from an oxytocin treatment. This oversight may in part be due to the enormous heterogeneity of ASD and the lack of methods to carefully probe the OXT system in human subjects. Animal models for ASD are valuable tools to clarify the implication of the oxytocin system in ASD and can help determine whether perturbation in this system should be considered in future clinical studies as stratifying biomarkers to inform targeted treatments in subgroups of individuals with ASD. In this chapter, we review the literature on genetic- and environmental-based animal models for ASD, in which perturbations in the oxytocin system and/or the effect of oxytocin administration on the ASD-associated phenotype have been investigated.
PMID:28864977
DOI:10.1007/7854_2017_15

24 août 2017

L'élévation du numéro de copie des gènes 22q11.2 arrête la maturation développementale de la capacité de la mémoire de travail et la neurogenèse de l'hippocampe chez les adultes

Aperçu: G.M.
La capacité de mémoire de travail, une composante essentielle de la fonction exécutive, s'élargit développementalement depuis l'enfance jusqu'à l'âge adulte. Des anomalies dans ce processus de développement sont observées chez les personnes avec un diagnostic de "trouble du spectre de l'autisme (TSA), dans la schizophrénie et les déficiences intellectuelles (DI), impliquant ce processus atypique dans la trajectoire des troubles neuropsychiatriques du développement.  
Cependant, les substrats cellulaires et neuronaux sous-jacents à ce processus ne sont pas compris. La duplication et la triplication de la variation du nombre de copies de 22q11.2 sont associées de façon constante et solide aux déficits cognitifs du TSA et de la DI chez les humains, et la surexpression des petits segments 22q11.2 récapitule les aspects dimensionnels des troubles neuropsychiatriques du développement chez la souris.  
En utilisant une approche d'expression génique sélective par type de région et de cellule, les chercheurs ont démontré que les élévations des nombres de copies de deux gènes (COMT, Tbx1), codés dans les deux petits segments 22q11.2 dans l'hippocampe, empêche la maturation du développement de la capacité de mémoire de travail chez la souris. 
Ces données fournissent une preuve de l'hypothèse nouvelle selon laquelle les élévations des nombres de copies de ces gènes 22q11.2 modifient la trajectoire développementale de la capacité de la mémoire de travail via une neurogénèse adulte sous-optimale dans l'hippocampe.

Mol Psychiatry. 2017 Aug 22. doi: 10.1038/mp.2017.158.

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis

Author information

1
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.
2
Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
3
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
4
Research Institute, Shiga Medical Center, Moriyama-shi, Shiga, Japan.
5
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
6
Department of Epidemiology &Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
7
Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan.
8
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
9
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.

Abstract

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.Molecular Psychiatry advance online publication, 22 August 2017; doi:10.1038/mp.2017.158.
PMID:28827761
DOI:10.1038/mp.2017.158

18 août 2017

Une revue systématique de la qualité de vie des adultes sur le "spectre de l'autisme"

Aperçu: G.M.
Le " trouble du spectre de l'autisme" est associé à des conditions coexistantes qui peuvent nuire à la qualité de vie d'un individu. Aucune étude systématique de la qualité de vie des adultes sur le spectre de l'autisme n'a été menée.  
Les objectifs des chercheurs étaient les suivants: 
  1. examiner les preuves concernant la qualité de vie des adultes sur le spectre autistique; 
  2. évaluer de manière critique la pratique actuelle dans l'évaluation de la qualité de vie des adultes sur le spectre de l'autisme. 
Sur un total de 827 études identifiées; 14 ont été incluses.
Une seule mesure de qualité de vie conçue pour être utilisée avec la population générale du spectre autistique a été identifiée.  
La qualité de vie des adultes sur le spectre de l'autisme est inférieure à celle des adultes au développement typique, lorsqu'elle est mesurée avec des outils conçus pour la population générale.
Il n'existe pas d'outils de mesure de qualité de vie spécifiques au "trouble du spectre de l'autisme" validés pour être utilisés avec des échantillons représentatifs d'adultes sur le spectre de l'autisme.
Il est urgent de développer des mesures robustes de la qualité de vie des adultes autistes.

Autism. 2017 Aug 1:1362361317714988. doi: 10.1177/1362361317714988.

A systematic review of quality of life of adults on the autism spectrum

Author information

1
Newcastle University, UK.

Abstract

Autism spectrum disorder is associated with co-existing conditions that may adversely affect an individual's quality of life. No systematic review of quality of life of adults on the autism spectrum has been conducted. Our objectives were as follows: (1) review the evidence about quality of life for adults on the autism spectrum; (2) critically appraise current practice in assessing quality of life of adults on the autism spectrum. We searched bibliographic databases and other literature to identify studies using a direct measure of quality of life of adults on the autism spectrum. Hand searching of reference lists, citation searching and personal communication with field experts were also undertaken. In total, 827 studies were identified; 14 were included. Only one quality of life measure designed for use with the general autism spectrum population was identified. Quality of life of adults on the autism spectrum is lower than that of typically developing adults, when measured with tools designed for the general population. There are no comprehensive autism spectrum disorder-specific quality of life measurement tools validated for use with representative samples of adults on the autism spectrum. There is a pressing need to develop robust measures of quality of life of autistic adults.

PMID:28805071
DOI:10.1177/1362361317714988

14 août 2017

L'inhibition de l'imitation chez les enfants avec un syndrome de Tourette

Aperçu: G.M.
L'échopraxie, c'est-à-dire l'imitation ouverte et automatique des actions d'autres personnes, est fréquente chez les "patients" avec un diagnostic de syndrome de Gilles de la Tourette, de "trouble du spectre de l'autisme" et chez ceux qui ont des lésions frontales. 
Bien que les tâches de temps de réaction systématique aient confirmé une augmentation de l'imitation automatique dans les deux derniers groupes, les patients adultes avec un syndrome de Tourette semblent compenser les tendances d'imitation automatiques par un ralentissement général des temps de réponse.  
Les résultats suggèrent que les enfants atteints du syndrome de Tourette utilisent déjà des stratégies d'inhibition différentes ou supplémentaires par rapport aux enfants en bonne santé.


J Neuropsychol. 2017 Aug 12. doi: 10.1111/jnp.12132.

Imitation inhibition in children with Tourette syndrome

Author information

1
Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Germany.
2
Department of Psychology, University of Southampton, UK.
3
Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany.
4
Department of Human Resources, Health and Social Affairs, University of Applied Sciences, Cologne, Germany.
5
Department of Neurology, Julius-Maximilians-University, Würzburg, Germany.
6
Department of Experimental Psychology, Ghent University, Belgium.

Abstract

OBJECTIVE:

Echopraxia, that is, the open and automatic imitation of other peoples' actions, is common in patients with Gilles de la Tourette syndrome, autism spectrum disorder, and also those with frontal lobe lesions. While systematic reaction time tasks have confirmed increased automatic imitation in the latter two groups, adult patients with Tourette syndrome appear to compensate for automatic imitation tendencies by an overall slowing in response times. However, whether children with Tourette syndrome are already able to inhibit automatic imitation tendencies has not been investigated.

METHOD:

Fifteen children with Tourette syndrome and 15 healthy children (aged 7-12 years) performed an imitation inhibition paradigm. Participants were asked to respond to an auditory cue by lifting their index finger or their little finger. Participants were simultaneously presented with either compatible or incompatible visual stimuli.

RESULTS:

Overall responses in children with Tourette syndrome were slower than in healthy children. Although responses were faster in compatible than in incompatible trials in both groups, this 'interference effect' was smaller in children with Tourette syndrome.

CONCLUSIONS:

Children with Tourette syndrome have a smaller interference effect than healthy children, indicating an enhanced ability to behaviourally control automatic imitation tendencies at the cost of reacting slower. The results suggest that children with Tourette syndrome already employ different or additional inhibition strategies compared to healthy children.

PMID:28801946
DOI:10.1111/jnp.12132

Symptômes précoces d'autisme chez les nourrissons avec une sclérose tubéreuse complexe

Aperçu: G.M.
La sclérose tubéreuse complexe (TSC) est un syndrome génétique autosomique dominant  qui confère un risque significativement augmenté pour le "trouble du spectre de l'autisme" (TSA), avec 50 à 60% des nourrissons ayant des critères de réunion de TSC pour le TSA à l'âge de 3 ans.  
Dans une étude antérieure de la cohorte longitudinale actuelle, l'équipe a constaté que les nourrissons avec TSC qui développent un TSA (TSC / ASD) montrent des capacités cognitives diminuées qui divergent des nourrissons avec TSC et sans TSA (TSC / no ASD). Le travail a été étendu en se demandant si les nourrissons TSC / TSA (n = 13) différaient des TSC / no ASD (n = 10) et des nourrissons à faible risque de développement et sans TSA (LR; n = 21) dans leur communication sociale au cours de la première année de vie.
Les chercheurs ont examiné les premiers signes de "trouble du spectre de l'autisme" (TSA) chez les nourrissons avec une sclérose tubéreuse complexe (environ 50%) répondant aux critères de TSA à l'âge de 3 ans. Les nourrissons avec TSC et TSA ont montré des déficits dans les comportements de communication sociale à l'âge de 9 mois qui se distinguent clairement des comportements chez les nourrissons avec TSC qui ne développent pas de TSA et chez les nourrissons à faible risque. 
 Les résultats confirment l'importance du dépistage et de l'intervention précoce des TSA pour les nourrissons avec TSC.

Autism Res. 2017 Aug 11. doi: 10.1002/aur.1846.

Early autism symptoms in infants with tuberous sclerosis complex

Author information

1
UCLA Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, 760 Westwood Plaza, Los Angeles, CA, 90095.
2
Telethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, WA, 6008, Australia.
3
Division of Pediatric Neurology, UCLA Mattel Children's Hospital, David Geffen School of Medicine, 10833 Le Conte Ave, MDCC Room 22-474, Los Angeles, CA, 90095.
4
Department of Neurology, Boston Children's Hospital, Translational Neuroscience Center, 300 Longwood Avenue, Boston, MA, 02115.
5
Division of Developmental Medicine, Boston Children's Hospital, Harvard Medical School & Harvard Graduate School of Education, Harvard University, 1 Autumn Street, Boston, MA, 02215.

Abstract

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic syndrome that confers significantly increased risk for autism spectrum disorder (ASD), with 50-60% of infants with TSC meeting criteria for ASD by 3 years of age. In a previous study of the current longitudinal cohort, we found that infants with TSC who develop ASD (TSC/ASD) evidence decreased cognitive abilities that diverge from infants with TSC and no ASD (TSC/no ASD). We extended this work by asking whether TSC/ASD infants (n = 13) differed from TSC/no ASD infants (n = 10) and infants with low developmental risk and no ASD (LR; n = 21) in their social communication functioning during the first year of life. We measured early ASD symptoms with the Autism Observation Scale for Infants (AOSI) at 9 and 12 months of age. At both ages, infants in the TSC/ASD group had significantly higher AOSI total scores than infants in the TSC/no ASD and LR groups, which were not fully explained by differences in cognitive abilities. Several items on the AOSI at both ages were predictive of ASD outcome, particularly those representing core social communication deficits (e.g., social referencing). Our findings signal the need for further study of this population within the first year and provide strong justification for early identification and early intervention targeting social communication skills in infants with TSC. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

LAY SUMMARY:

We examined early signs of autism spectrum disorder (ASD) in infants with tuberous sclerosis complex (TSC), approximately 50% of whom will meet criteria for ASD by age 3. Infants with TSC and ASD showed deficits in social communication behaviors by 9 months of age that were clearly distinguishable from behaviors in infants with TSC who do not develop ASD and low risk infants. Results support the importance of early ASD screening and intervention for infants with TSC.

PMID:28801991
DOI:10.1002/aur.1846

03 août 2017

Taux, répartition et implications des mutations de la mosaïque poszygotique dans le trouble du spectre de l'autisme

Aperçu: G.M.
Les chercheurs ont systématiquement analysé les mutations postzygotiques (PZM) dans des séquences entières de la plus grande collection de trios (5 947) avec le trouble du spectre de l'autisme (TSA) disponible, y compris 282 trios non publiés, et effectué un re-séquencement en utilisant de multiples technologies indépendantes. Ils ont identifié 7,5% des mutations de novo en tant que PZM, dont 83,3% n'ont pas été décrits dans des études antérieures.
Les PZM constituent une proportion importante de mutations de novo et contribuent de manière importante au risque de TSA. 

Nat Neurosci. 2017 Jul 17. doi: 10.1038/nn.4598.

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Author information

1
Division of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts, USA.
2
Departments of Pediatrics and Neurology, Harvard Medical School, Boston, Massachusetts, USA.
3
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
5
Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, United Arab Emirates.
6
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai,New York, New York, USA.
7
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
8
Department of Psychiatry, Center For Excellence in Autism Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
9
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
10
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
11
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Madrid, Spain.
12
Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado-Plataforma de Recursos Biomoleculares y Bioinformaticos-Instituto de Salud Carlos III (CeGen-PRB2-ISCIII), Santiago de Compostela, Spain.
13
Grupo de Medicina Xenomica, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Santiago de Compostela, Spain.
14
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
15
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
16
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
17
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
18
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
19
Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
20
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
21
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
22
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
23
Program in Genetics and Genome Biology (GGB), The Hospital for Sick Children, Toronto, Ontario, Canada.
24
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
25
McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.

Abstract

We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.
PMID:28714951
DOI:10.1038/nn.4598