Comparaison transcriptomique du sang chez les personnes avec et sans diagnostic de trouble du spectre de l'autisme: une méga-analyse d'échantillons combinés

Aperçu: G.M.

Les études fondées sur les puces à ADN sur le sang comparant les personnes avec un diagnostic de trouble du spectre de l'autisme (TSA) et des personnes au développement typique aident à caractériser les différences dans les fonctions de cellules immunitaires circulantes et proposent un biomarqueur potentiel.

Am J Med Genet B Neuropsychiatr Genet. 2017 Apr;174(3):181-201. doi: 10.1002/ajmg.b.32511. Epub 2016 Nov 11.

Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined-samples mega-analysis

Tylee DS¹, Hess JL¹, Quinn TP¹, Barve R¹, Huang H^2,3, Zhang-James Y¹, Chang J⁴, Stamova BS⁵, Sharp FR⁵, Hertz-Picciotto I⁶, Faraone SV^1,7, Kong SW⁸, Glatt SJ¹.

Author information

1

Departments of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe Lab), SUNY Upstate Medical University, Syracuse, New York.

2

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.

3

Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

4

Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New York.

5

Department of Neurology, UC Davis School of Medicine, Sacramento, California.

6

Department of Public Health Sciences and UC Davis MIND Institute, School of Medicine, Davis, California.

7

K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.

8

Department of Pediatrics, Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Abstract

Blood-based microarray studies comparing individuals affected with autism spectrum disorder (ASD) and typically developing individuals help characterize differences in circulating immune cell functions and offer potential biomarker signal. We sought to combine the subject-level data from previously published studies by mega-analysis to increase the statistical power. We identified studies that compared ex vivo blood or lymphocytes from ASD-affected individuals and unrelated comparison subjects using Affymetrix or Illumina array platforms. Raw microarray data and clinical meta-data were obtained from seven studies, totaling 626 affected and 447 comparison subjects. Microarray data were processed using uniform methods. Covariate-controlled mixed-effect linear models were used to identify gene transcripts and co-expression network modules that were significantly associated with diagnostic status. Permutation-based gene-set analysis was used to identify functionally related sets of genes that were over- and under-expressed among ASD samples. Our results were consistent with diminished interferon-, EGF-, PDGF-, PI3K-AKT-mTOR-, and RAS-MAPK-signaling cascades, and increased ribosomal translation and NK-cell related activity in ASD. We explored evidence for sex-differences in the ASD-related transcriptomic signature. We also demonstrated that machine-learning classifiers using blood transcriptome data perform with moderate accuracy when data are combined across studies. Comparing our results with those from blood-based studies of protein biomarkers (e.g., cytokines and trophic factors), we propose that ASD may feature decoupling between certain circulating signaling proteins (higher in ASD samples) and the transcriptional cascades which they typically elicit within circulating immune cells (lower in ASD samples). These findings provide insight into ASD-related transcriptional differences in circulating immune cells. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.

PMID: 27862943

DOI: 10.1002/ajmg.b.32511

Une revue complète systématique et une méta-analyse des interventions pharmacologiques et des suppléments alimentaires dans l'autisme chez l'enfant: modérateurs de la réponse au traitement et recommandations pour des recherches futures

Aperçu: G.M.

Les troubles du spectre de l'autisme (TSA) sont des conditions neurodéveloppementales multipartites et multifactorielles, caractérisées par des altérations de la communication et de l'interaction sociales, et des comportements, des intérêts ou des activités restreints et répétitifs. Les options de traitement pour améliorer les symptômes des TSA sont limitées.

Les recherches bibliographiques sur EMBASE, MEDLINE et PsycINFO ont permis d'identifier 43 études pour l'évaluation qualitative de la caractérisation de base des participants et 37 études pour l'analyse quantitative des modérateurs de la réponse au traitement.

Peu d'essais ont rapporté des caractéristiques de base adéquates pour permettre une analyse détaillée de la réponse au traitement. Il faut tenir compte de la situation géographique, de la gravité de base et de la fonction intellectuelle pour assurer la généralisation des résultats. L'utilisation de marqueurs biologiques et de corrélats dans les essais TSA en est encore à ses balbutiements.

Il est grandement nécessaire d'améliorer l'application de la caractérisation de base et l'incorporation de marqueurs biologiques et corrélés pour permettre la sélection des participants en sous-groupes homogènes et pour documenter la réponse au traitement dans les TSA.  

Psychol Med. 2017 May;47(7):1323-1334. doi: 10.1017/S0033291716003457. Epub 2017 Jan 16.

A comprehensive systematic review and meta-analysis of pharmacological and dietary supplement interventions in paediatric autism: moderators of treatment response and recommendations for future research

Masi A¹, Lampit A², DeMayo MM¹, Glozier N¹, Hickie IB¹, Guastella AJ¹.

Author information

1

Autism Clinic for Translational Research,Brain and Mind Centre,Central Clinical School,Sydney Medical School,University of Sydney,Camperdown,NSW,Australia.

2

Regenerative Neuroscience Group,Brain and Mind Centre,University of Sydney,Camperdown,NSW,Australia.

Abstract

BACKGROUND:

Autism spectrum disorders (ASDs) are pervasive and multifactorial neurodevelopmental conditions, characterized by impairments in social communication and interaction, and restricted, repetitive patterns of behaviour, interests or activities. Treatment options to ameliorate symptoms of ASDs are limited. Heterogeneity complicates the quest for personalized medicine in this population. Our aim was to investigate if there are baseline characteristics of patients that moderate response or trial design features that impede the identification of efficacious interventions for ASDs.

METHOD:

Literature searches of EMBASE, MEDLINE and PsycINFO identified 43 studies for qualitative assessment of baseline characterization of participants and 37 studies for quantitative analysis of moderators of treatment response. Criteria included blinded randomized controlled trials (RCTs) in paediatric ASD, with at least 10 participants per arm or 20 overall, of oral treatments, including pharmacological interventions and dietary supplements.

RESULTS:

Random-effects meta-analysis of 1997 participants (81% male) identified three moderators associated with an increase in treatment response: trials located in Europe and the Middle-East; outcome measures designated primary status; and the type of outcome measure. Inconsistent reporting of baseline symptom severity and intellectual functioning prevented analysis of these variables. Qualitative synthesis of baseline characteristics identified at least 31 variables, with only age and gender reported in all trials. Biological markers were included in six RCTs.

CONCLUSIONS:

Few trials reported adequate baseline characteristics to permit detailed analysis of response to treatment. Consideration of geographical location, baseline severity and intellectual function is required to ensure generalizability of results. The use of biological markers and correlates in ASD trials remains in its infancy. There is great need to improve the application of baseline characterization and incorporation of biological markers and correlates to permit selection of participants into homogeneous subgroups and to inform response to treatment in ASD.

PMID: 28091344

DOI: 10.1017/S0033291716003457

Les effets de l'infection prénatale H1N1 chez E16 sur les systèmes de signalisation FMRP, glutamate, GABA et Réelin dans le développement du cervelet murin

Aperçu: G.M.

L'infection virale prénatale a été identifiée comme un facteur de risque potentiel pour le développement de troubles neurodéveloppementaux tels que la schizophrénie et l'autisme.  

L'étude a caractérisé les profils de développement de marqueurs sélectionnés pour ces systèmes dans des cérébelles de souris nées de souris enceintes infectées par le virus de la grippe humaine (H1N1) .

Le cervelet a été choisi du fait des preuves émergentes selon lesquelles il joue un rôle dans l'apprentissage, la mémoire et le traitement émotionnel, tous perturbés dans l'autisme et la schizophrénie.

L'étude fournit des preuves de perturbation de la FMRP, de la glutamatérgie et de la signalisation de Reelin chez la progéniture de souris exposée qui explique les multiples anomalies cérébrales observées dans ce modèle animal.  

J Neurosci Res. 2017 May;95(5):1110-1122. doi: 10.1002/jnr.23949. Epub 2016 Oct 13.

The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum

Fatemi SH^1,2, Folsom TD¹, Liesch SB¹, Kneeland RE¹, Karkhane Yousefi M^1,3, Thuras PD⁴.

Author information

1

Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.

2

Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota.

3

Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.

4

VA Medical Center, Department of Psychiatry, Minneapolis, Minnesota.

Abstract

Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development. The cerebellum was selected in light of emerging evidence that it plays roles in learning, memory, and emotional processing-all of which are disrupted in autism and schizophrenia. We identified unique patterns of gene and protein expression at birth (postnatal day 0 [P0]), childhood (P14), adolescence (P35), and young adulthood (P56) in both exposed and control mouse progeny. We also identified significant differences in protein expression for FMRP, very-low-density lipoprotein receptor, and glutamic acid decarboxylase 65 and 67 kDa proteins at specific postnatal time points in cerebella of the offspring of exposed mice. Our results provide evidence of disrupted FMRP, glutamatergic, and Reelin signaling in the exposed mouse offspring that explains the multiple brain abnormalities observed in this animal model. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.

PMID: 27735078

PMCID: PMC5352480 [Available on 2017-11-01]

DOI: 10.1002/jnr.23949

Pratiques et résultats de l'auto-traitement avec des helminthes basés sur les observations des médecins

Aperçu: G.M.

L'utilisation réussie d'helminthes en tant qu'agents thérapeutiques pour résoudre la maladie inflammatoire a été rapportée pour la première fois il y a 40 ans. Ces organismes pourraient traiter efficacement un large éventail de maladies inflammatoires, y compris des allergies, des troubles auto-immuns et des troubles neuropsychiatriques associés à l'inflammation. Cinq médecins surveillant plus de 700 patients auto-traitants ont été interviewés.

Environ 57% des patients auto-traitants observés par les médecins de l'étude avaient un autisme. Les médecins ont rapporté que la majorité leurs patients avec un diagnostic de TSA et des co-morbidités associées à l'inflammation ont répondu favorablement à la thérapie avec l'un ou l'autre des deux organismes les plus populaires actuellement utilisés par les auto-traitements, Hymenolepis diminuta et Trichuris suis. Cependant, environ 1% des patients pédiatriques ont souffert de douleurs gastro-intestinales sévères avec l'utilisation de H. diminuta, bien que les symptômes aient été résolus avec un médicament anti-helminthique. 

L'exposition aux helminthes n'a apparemment pas affecté la compréhension réduite des situations sociales qui est la marque distinctive de l'autisme. 

J Helminthol. 2017 May;91(3):267-277. doi: 10.1017/S0022149X16000316. Epub 2016 May 31.

Practices and outcomes of self-treatment with helminths based on physicians' observations

Liu J¹, Morey RA², Wilson JK³, Parker W¹.

Author information

1

Department of Surgery,Duke University Medical Center,Durham, NC 27710,USA.

2

Department of Psychiatry and Behavioral Sciences,Duke University Medical Center,Durham, NC 27710,USA.

3

Department of Sociology,University of Central Arkansas,Conway, AR, 72035,USA.

Abstract

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

PMID: 27240605

DOI: 10.1017/S0022149X16000316

Le régime kétogène et les troubles neurologiques de l'enfance autres que l'épilepsie: une vue d'ensemble

Aperçu: G.M.

Au cours des dernières années, le régime kétogène (KD) a été utilisé expérimentalement dans divers troubles neurologiques de l'enfance tels que les mitochondriopathies, l'hémiplégie alternée de l'enfance (AHC), les tumeurs cérébrales, la migraine et le trouble du spectre de l'autisme (TSA).

L'étude visait à analyser comment le KD peut cibler ces différentes conditions médicales, mettant en évidence les possibles mécanismes impliqués.

Le KD pourrait améliorer les compétences cognitives et sociales dans un sous-ensemble d'enfants avec un diagnostic de TSA

Expert Rev Neurother. 2017 May;17(5):461-473. doi: 10.1080/14737175.2017.1260004. Epub 2016 Nov 21.

Ketogenic diet and childhood neurological disorders other than epilepsy: an overview

Verrotti A¹, Iapadre G¹, Pisano S², Coppola G³.

Author information

1

a Department of Pediatrics , University of L'Aquila, San Salvatore Hospital , L'Aquila , Italy.

2

b Department of Child and Adolescent Neuropsychiatry , University of Salerno , Salerno , Italy.

3

c Department of Child Neuropsychiatry , University of Salerno , Salerno , Italy.

Abstract

INTRODUCTION:

In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.

PMID: 27841033

DOI: 10.1080/14737175.2017.1260004

La signalisation placentaire interleukine-6 contrôle le développement et le comportement du cerveau du foetus

Aperçu: G.M.

Des études épidémiologiques montrent que l'activation immunitaire maternelle (MIA) pendant la grossesse est un facteur de risque pour l'autisme. Cependant, les mécanismes de la MIA affectant le développement du cerveau et les comportements chez les descendants restent mal décrits.

Les résultats de l'étude démontrent que l'activation de l'IL-6 dans le placenta est nécessaire pour transmettre les signaux inflammatoires au cerveau fœtal et les comportements et les neuropathologies affectant le trouble neuro-dévelopemental. 

Brain Behav Immun. 2017 May;62:11-23. doi: 10.1016/j.bbi.2016.11.007. Epub 2016 Nov 9.

The placental interleukin-6 signaling controls fetal brain development and behavior

Wu WL¹, Hsiao EY², Yan Z³, Mazmanian SK⁴, Patterson PH⁵.

Author information

1

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: wlwu@caltech.edu

2

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA; Department of Integrative Biology & Physiology, University of California, Los Angeles, 610 Charles E. Young Drive, Los Angeles, CA 90095, USA. Electronic address: ehsiao@ucla.edu.

3

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: Zihao_Yan@hms.harvard.edu.

4

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.

5

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: php@caltech.edu.

Abstract

Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism. However, mechanisms for how MIA affects brain development and behaviors in offspring remain poorly described. To determine whether placental interleukin-6 (IL-6) signaling is required for mediating MIA on the offspring, we generated mice with restricted deletion of the receptor for IL-6 (IL-6Rα) in placental trophoblasts (Cyp19-Cre⁺;Il6ra^fl/fl), and tested offspring of Cyp19-Cre⁺;Il6ra^fl/fl mothers for immunological, pathological and behavioral abnormalities following induction of MIA. We reveal that MIA results in acute inflammatory responses in the fetal brain. Lack of IL-6 signaling in trophoblasts effectively blocks MIA-induced inflammatory responses in the placenta and the fetal brain. Furthermore, behavioral abnormalities and cerebellar neuropathologies observed in MIA control offspring are prevented in Cyp19-Cre⁺;Il6ra^fl/fl offspring. Our results demonstrate that IL-6 activation in placenta is required for relaying inflammatory signals to the fetal brain and impacting behaviors and neuropathologies relevant to neurodevelopmental disease.

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID: 27838335

DOI: 10.1016/j.bbi.2016.11.007

L'amorçage développemental microglial dans le cortex temporel post-mortem dans le spectre de l'autisme

Aperçu: G.M.

La microglie peut se transformer en différentes morphologies complexes en fonction du microenvironnement du système nerveux central (SNC). Les morphologies distinctes sont en corrélation avec des fonctions spécifiques et peuvent indiquer l'état pathophysiologique du SNC. Les études post-mortem antérieures du trouble du spectre autistique (ASD) ont montré une neuroinflammation dans les TSA indiquée par une augmentation de la densité microgliale.Ces changements dans la densité de la microglie peuvent s'accompagner de changements dans le phénotype de la microglie mais la contribution individuelle des différents phénotypes de la microglie à la pathophysiologie des TSA reste incertaine. 

Les résultats témoignent d'un changement dans le phénotype microglial qui peut indiquer une plasticité synaptique altérée et une vulnérabilité chronique aux réponses immunitaires exagérées. 

Brain Behav Immun. 2017 May;62:193-202. doi: 10.1016/j.bbi.2017.01.019. Epub 2017 Feb 1.

Developmental microglial priming in postmortem autism spectrum disorder temporal cortex

Lee AS¹, Azmitia EC², Whitaker-Azmitia PM³.

Author information

1

Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA; Department of Biology, New York University, New York, NY 10003, USA; Max Planck Institute for Biological Cybernetics, 72076 Tuebingen, Germany. Electronic address: Andrew.s.lee@alumni.stonybrook.edu

2

Department of Biology, New York University, New York, NY 10003, USA.

3

Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.

Abstract

Microglia can shift into different complex morphologies depending on the microenvironment of the central nervous system (CNS). The distinct morphologies correlate with specific functions and can indicate the pathophysiological state of the CNS. Previous postmortem studies of autism spectrum disorder (ASD) showed neuroinflammation in ASD indicated by increased microglial density. These changes in the microglia density can be accompanied by changes in microglia phenotype but the individual contribution of different microglia phenotypes to the pathophysiology of ASD remains unclear. Here, we used an unbiased stereological approach to quantify six structurally and functionally distinct microglia phenotypes in postmortem human temporal cortex, which were immuno-stained with Iba1. The total density of all microglia phenotypes did not differ between ASD donors and typically developing individual donors. However, there was a significant decrease in ramified microglia in both gray matter and white matter of ASD, and a significant increase in primed microglia in gray matter of ASD compared to typically developing individuals. This increase in primed microglia showed a positive correlation with donor age in both gray matter and white of ASD, but not in typically developing individuals. Our results provide evidence of a shift in microglial phenotype that may indicate impaired synaptic plasticity and a chronic vulnerability to exaggerated immune responses.

Copyright © 2017 Elsevier Inc. All rights reserved.

PMID: 28159644

DOI: 10.1016/j.bbi.2017.01.019

Analyse des variations de nombre de copies chez les personnes avec un diagnostic d'autisme à l'aide de techniques cytogénétiques et MLPA: rapport sur les duplications 16p13.1p13.3 et 10q26.3

Aperçu: G.M.

L'autisme est un trouble neuropsychiatrique commun affectant 1 enfant sur 68. Les variations de nombre de copies (CNV) sont connues pour être des facteurs majeurs du trouble du spectre  de l'autisme. Dans cette étude, le carotypage et MLPA ont été utilisé pour détecter les VNC chez 50 personnes iraniennes avec un diagnostic de TSA.  

Les résultats suggèrent qu'il pourrait être possible d'obtenir des informations utiles en utilisant la technique MLPA mais ne peut pas être utilisé comme outil de diagnostic unique pour l'autisme.

Int J Mol Cell Med. 2016 Fall;5(4):236-245. Epub 2016 Dec 5.

Analysis of Copy Number Variations in Patients with Autism Using Cytogenetic and MLPA Techniques: Report of 16p13.1p13.3 and 10q26.3 Duplications

Ghasemi Firouzabadi S¹, Vameghi R², Kariminejad R³, Darvish H⁴, Banihashemi S¹, Firouzkouhi Moghaddam M⁵, Jamali P⁶, Farbod Mofidi Tehrani H⁷, Dehghani H¹, Raeisoon MR⁸, Narooie-Nejad M⁹, Jamshidi J¹⁰, Tafakhori A¹¹, Sadabadi S¹², Behjati F¹.

Author information

1

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

2

Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

3

Kariminejad- Najmabadi Pathology and Genetics Center, Tehran, Iran.

4

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5

Child and Adolescent Psychiatry Department, Zahedan University of Medical Sciences, Zahedan, Iran.; Research Center for Children and Adolescents Health, Zahedan University of Medical Sciences, Zahedan, Iran.

6

Shahroud Welfare Organization, Shahroud, Iran.

7

Health Psychology Department, Edalat University, Tehran, Iran.

8

Psychiatry and Behavioral Science Research Center, Department of Social Medicine, Medicine Faculty, Birjand University of Medical Sciences, Birjand, Iran.

9

Genetics of Non- Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

10

Non-Communicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

11

Department of Neurology, School of Medicine, Imam Khomeini Hospital and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.

12

Bahar ducation and Rehabilitation Center for the handicapped, Tehran, Iran.

Abstract

Autism is a common neuropsychiatric disorder affecting 1 in 68 children. Copy number variations (CNVs) are known to be major contributors of autism spectrum disorder (ASD). There are different whole genome or targeted techniques to identify CNVs in the patients including karyotyping, multiplex ligation-dependent probe amplification (MLPA) and array CGH. In this study, we used karyotyping and MLPA to detect CNVs in 50 Iranian patients with autism. GTG banding and 4 different MLPA kits (2 subtelomeric and 2 autism kits) were utilized. To elevate our detection rate, we selected the sporadic patients who had additional clinical features including intellectual disability, seizure, attention deficit hyperactivity disorder, and abnormal head circumference. Two out of 50 patients (4%) showed microscopic chromosome abnormalities and 5 out of 50 (10%) demonstrated copy number gains or losses using MLPA kits. Including one overlapping result between karyotype and MLPA techniques, our overall detection rate was 6 out of 50 (12%). Three out of 6 CNVs were de novo and three others were paternally inherited. Two of CNVs detected by karyotyping and MLPA tests were 16p13.1q13.3 and 10q26.3 duplications, respectively. For these two CNVs genotype and phenotype of the patients were compared with other studies. Although the pathogenicity of cytogenetic results was certain, most of MLPA results needed to be better refined using other more accurate techniques such as array CGH. Our findings suggest that it might be possible to obtain some useful information using MLPA technique but it cannot be used as a single diagnostic tool for the autism.

PMID: 28357200

Gènes candidats pour la susceptibilité héréditaire à l'autiste dans la population libanaise

Aperçu: G.M.

Le trouble du spectre de l'autisme (TSA) se caractérise par des comportements rituels répétitifs et une communication verbale / non verbale altérée. Beaucoup de gènes de sensibilité aux TSA impliqués dans les voies neuronales / développement du cerveau ont été identifiés. La population libanaise est idéale pour découvrir des gènes récessifs en raison de l'ascendance partagée et d'un taux élevé de mariages consanguins.

 Bien qu'une légère augmentation du nombre ait été observée chez les personnes avec un diagnostic de TSA et les membres de la famille par rapport aux témoins, il n'y avait pas de différences significatives dans les fréquences alléliques entre les personnes avec un diagnostic de TSA et les témoins (C / TTCTG: valeur γ2 = 0,014; p = 0,904). 

 Le polymorphisme CNTNAP2 identifié dans cette population, par conséquent, n'est pas lié au phénotype TSA.

Cliquez ici pour accéder à l'intégralité de l'article en anglais

Sci Rep. 2017 Mar 30;7:45336. doi: 10.1038/srep45336.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

Kourtian S^1,2, Soueid J¹, Makhoul NJ¹, Guisso DR¹, Chahrour M³, Boustany RN^1,4.

Author information

1

American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Lebanon.

2

Department of Biological and Environmental Sciences, Faculty of Science, Beirut Arab University, Lebanon.

3

Eugene McDermott Center for Human Growth and Development, Departments of Neuroscience and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

4

Biochemistry and Molecular Genetics, American university of Beirut, Lebanon.

Abstract

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ² value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.

PMID: 28358038

DOI: 10.1038/srep45336

Thérapie par l'équitation pour une personne sourde-aveugle activée par une interface haptique

Aperçu: G.M.

L'étude présente une interface haptique pour aider les sourds-aveugles à pratiquer l'équitation comme activité récréative et thérapeutique.

es réponses aux questionnaires remplis par le cavalier, la famille et l'instructeur montrent que notre technique donne au coureur un plus grand sens de l'indépendance et plus de joie par rapport à l'équitation standard où l'instructeur marche avec le cheval. 

Assist Technol. 2017 Mar 27:1-8. doi: 10.1080/10400435.2017.1288178

Horseback riding therapy for a deafblind individual enabled by a haptic interface

Ogrinc Ms M^1,2, Farkhatdinov PhD I^1,3, Walker Ms R², Burdet E¹.

Author information

1

a Department of Bioengineering , Imperial College of Science, Technology and Medicine , London , United Kingdom.

2

b Shadow Robot Company LTD , London , United Kingdom.

3

c School of Electronic Engineering and Computer Science , Queen Mary University of London , London , United Kingdom.

Abstract

We present a haptic interface to help deafblind people to practice horseback riding as a recreational and therapeutic activity. Horseback riding is a form of therapy which can improve self-esteem and sensation of independence. It has been shown to benefit people with various medical conditions-including autism. However, in the case of deafblind riders, an interpreter must stand by at all times to communicate with the rider by touch. We developed a simple interface that enables deafblind people to enjoy horseback riding while the instructor is remotely providing cues, which improves their independence. Experiments demonstrated that an autistic deafblind individual exhibits similar responses to navigational cues as an unimpaired rider. Motivation is an important factor in therapy, and is frequently determinant of its outcome; therefore, the user attitude toward the therapy methods is key. The answers to questionnaires filled by the rider, family, and the instructor show that our technique gives the rider a greater sense of independence and more joy compared to standard riding where the instructor is walking along with the horse.

PMID: 28346067

DOI: 10.1080/10400435.2017.1288178