Pubmed du 21/02/20

vendredi 21 février 2020

1. Bacchelli E, Cameli C, Viggiano M, Igliozzi R, Mancini A, Tancredi R, Battaglia A, Maestrini E. An integrated analysis of rare CNV and exome variation in Autism Spectrum Disorder using the Infinium PsychArray. Sci Rep ;2020 (Feb 21) ;10(1):3198.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex and heterogeneous genetic etiology. While a proportion of ASD risk is attributable to common variants, rare copy-number variants (CNVs) and protein-disrupting single-nucleotide variants (SNVs) have been shown to significantly contribute to ASD etiology. We analyzed a homogeneous cohort of 127 ASD Italian families genotyped with the Illumina PsychArray, to perform an integrated analysis of CNVs and SNVs and to assess their contribution to ASD risk. We observed a higher burden of rare CNVs, especially deletions, in ASD individuals versus unaffected controls. Furthermore, we identified a significant enrichment of rare CNVs intersecting ASD candidate genes reported in the SFARI database. Family-based analysis of rare SNVs genotyped by the PsychArray also indicated an increased transmission of rare SNV variants from heterozygous parents to probands, supporting a multigenic model of ASD risk with significant contributions of both variant types. Moreover, our study reinforced the evidence for a significant role of VPS13B, WWOX, CNTNAP2, RBFOX1, MACROD2, APBA2, PARK2, GPHN, and RNF113A genes in ASD susceptibility. Finally, we showed that the PsychArray, besides providing useful genotyping data in psychiatric disorders, is a valuable and cost-efficient tool for genic CNV detection, down to 10 kb.

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2. Cabet S, Lesca G, Labalme A, Portes VD, Guibaud L, Sanlaville D, Pons L. Novel truncating and missense variants extending the spectrum of EMC1-related phenotypes, causing autism spectrum disorder, severe global development delay and visual impairment. Eur J Med Genet ;2020 (Feb 21):103897.

The EMC1 gene, located on 1p36.13, encodes the subunit 1 of the endoplasmic reticulum-membrane protein complex, a highly conserved and ubiquitous multiprotein transmembrane complex. Pathogenic monoallelic and biallelic variants in EMC1 in humans have been reported only in six families, causing isolated visual impairment or in association with psychomotor retardation and cerebellar atrophy. We report a ten-year-old boy, born to unrelated parents, with early-onset severe global development delay due to novel EMC1 biallelic pathogenic variants. A truncating variant, p.(Tyr378*) and a missense variant, p.(Phe953Ser), located in exon 11 and 23 of EMC1 gene respectively, have been found by reanalysis of exome sequencing data. The proband’s phenotype included several signs that overlap with the phenotype of previously reported patients, associating severe global developmental delay, abnormal ophthalmological examination, and postnatal slow-down of the head circumference growth. Some distinguishing clinical signs were observed in comparison to patients from literature, such as autism spectrum disorder, absence of seizures, scoliosis or facial dysmorphic features, thus extending the spectrum of EMC1-related phenotypes. Similarly, brain MRI, performed at 2 years, showed normal cerebellar volume and structure, whereas cerebellar atrophy was described in literature. Moreover, difficulties of clinical differential diagnosis between EMC1-associated disease and other etiologies of global development delay support the importance of large-scale genetic investigations. Our diagnostic approach, through reanalysis of exome sequencing data, highlights the importance of reconsidering initial negative results for patients with a strong suspicion of genetic disease, and to update analytic pipelines in order to improve the diagnostic yield of exome sequencing.

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3. de Leeuw A, Happe F, Hoekstra RA. A Conceptual Framework for Understanding the Cultural and Contextual Factors on Autism Across the Globe. Autism Res ;2020 (Feb 21)

Autism research is heavily skewed toward western high-income countries. Culturally appropriate screening and diagnostic instruments for autism are lacking in most low- and middle-income settings where the majority of the global autism population lives. To date, a clear overview of the possible cultural and contextual factors that may affect the process of identifying and diagnosing individuals with autism spectrum disorders (ASD) is missing. This study aims to outline these factors by proposing a conceptual framework. A multidisciplinary review approach was applied to inform the development of the conceptual framework, combining a systematic review of the relevant autism research literature with a wider literature search spanning key texts in global mental health, cultural psychiatry, cross-cultural psychology, and intellectual disability research. The resulting conceptual framework considers the identification, help-seeking, and diagnostic process at four interrelated levels : (a) the expression ; (b) recognition ; (c) interpretation ; and (d) reporting of autism symptoms, and describes the cultural and contextual factors associated with each of these levels, including cultural norms of typical and atypical behavior, culture-specific approaches to parenting, mental health literacy, cultural beliefs, attitudes and stigma, as well as the affordability, availability, accessibility, and acceptability of services. This framework, mapping out the cultural and contextual factors that can affect the identification, help-seeking, and diagnosis of ASD may function as a springboard for the development of culturally appropriate autism screening and diagnostic instruments, and inform future cross-cultural autism research directions. The framework also has relevance for clinicians and policy makers aiming to improve support for underserved autism populations worldwide. LAY SUMMARY : The vast majority of autism research is conducted in western high-income settings. We therefore know relatively little of how culture and context can affect the identification, help-seeking, and diagnosis of autism across the globe. This study synthesizes what is known from the autism research literature and a broader literature and maps out how culture and context may affect (a) the expression, (b) recognition, (c) interpretation, and (d) reporting of autism symptoms. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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4. Geng L, Hamel F, Lewis D. Results of a Consumer Survey on the Effectiveness of a Nutritional Blend Reported on Autism Spectrum Disorder Symptoms, Apraxia, and Other Conditions Involving Motor and Speech Delays. Altern Ther Health Med ;2020 (Feb 21)

Background : The causes and cures for Autism Spectrum Disorders (ASDs), apraxia, and other conditions involving motor and speech delays remain speculative. To offset symptoms, many individuals will try integrative approaches, including making dietary changes and adding vitamins, minerals, and fish oil supplements. Primary Study Objective : The purpose of this study was to glean opinions about the effectiveness of specific food blends and nutrients on speech and motor impairments within a sample population of adults and children (N = 77) who self-report having communication delays and/or motor dysfunction symptoms, and who are among a population currently taking IQed (N = 632) nutritional composition. Methods/Design : A 28-point survey instrument was designed across key areas relating to symptoms of speech and motor abilities. Additional subquestions were included for descriptive summary and description statistical interpretation of the data. The Web-based survey was conducted on a sample population of adults and children (N = 77) who self-reported having communication delays and motor function symptoms, and who are among a population currently taking IQed (N = 632) nutritional composition, a whole food complete vitamin and meal replacement product. Setting : The survey was conducted via the Internet using SurveyMonkey (San Mateo, CA, USA). Participants : Consumers (or their caregiver) completed an online survey and answered questions about nutritional supplementation use and their opinion about product effectiveness on symptoms. A total of 88 individuals responded to the survey and 11 were excluded for incompletion of the survey. Included participants comprise 55 males and 22 females (N = 77) with a median age of 10.5 y and an age range from 2 to 70 y. Participants’ geographic location represent as 85.7% from the United States and 9 other countries (14.3%). Primary Outcome Measures : Effectiveness was measured based on participant ratings using a numeric rating scale to report on changes in symptoms for a defined period of use of the supplement. Results : Ninety-two percent of the survey respondents reported positive behavioral or physical changes when IQed formula was added to the diet, with most (64%) reporting positive changes within the first 2 wk. Difficulty with speech and communication was the highest reported area of difficulty for this population, afflicting 83.8% of respondents. After supplementation, expressive speech improved for 85.7% of the participants with the increased vocalizations (sounds, words) factor showing the highest observed improvement (88.1%) among all speech/communication factors combined. In all other categories, more than 67% of the survey takers reported improvements in all factors : speech (77.6%), oral motor skills (63.2%), receptive ability (69.6%), focus (65.1%), motor planning (77.6%), mood (62.3%), social skills (59.3%), and physical/behavioral health (47.3%), with any adverse effects reported in less than 1%. Conclusion : Consumers reported improvements in symptoms by use of a blended vitamin and mineral product (IQed Smart Nutrition composition). The implication for this study is to further research on alternative modalities of treatments for ASD and ASD-type conditions using natural food products, vitamin and mineral supplements, and Ayurvedic and botanical ingredients.

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5. Guerini FR, Bolognesi E, Chiappedi M, Mensi MM, Fumagalli O, Rogantini C, Zanzottera M, Ghezzo A, Zanette M, Agliardi C, Costa AS, Sotgiu S, Carta A, Al Daghri N, Clerici M. Vitamin D Receptor Polymorphisms Associated with Autism Spectrum Disorder. Autism Res ;2020 (Feb 21)

Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR) ; the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 x 10(-4) ; OR : 0.1, 95% CI : 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. LAY SUMMARY : Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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6. Hayes J, McCabe R, Ford T, Russell G. Drawing a line in the sand : affect and testimony in autism assessment teams in the UK. Sociol Health Illn ;2020 (Feb 21)

Diagnosis of autism in the UK is generally made within a multidisciplinary team setting and is primarily based on observation and clinical interview. We examined how clinicians diagnose autism in practice by observing post-assessment meetings in specialist autism teams. Eighteen meetings across four teams based in the south of England and covering 88 cases were audio-recorded, transcribed and analysed using thematic analysis. We drew out two themes, related to the way in which clinicians expressed their specialist disciplinary knowledge to come to diagnostic consensus : Feeling Autism in the Encounter ; and Evaluating Testimonies of Non-present Actors. We show how clinicians produce objective accounts through their situated practices and perform diagnosis as an act of interpretation, affect and evaluation to meet the institutional demands of the diagnostic setting. Our study contributes to our understanding of how diagnosis is accomplished in practice.

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7. Hochard KD, Pendrous R, Mari T, Flynn S. Examining the Relationship Between Autism Traits and Sleep Duration as Predictors of Suicidality. J Autism Dev Disord ;2020 (Feb 21)

Short sleep duration is a known risk factor for suicidality in the general population, yet it is unclear how short sleep interacts with autism traits in predicting suicidality. In this cross-sectional online study, a general population sample (N = 650) completed measures assessing autism traits, suicidal ideation, and sleep duration. Moderated hierarchical regressions demonstrated that higher autism traits and shorter sleep were independent predictors of increased suicide ideation. However, sleep duration did not significantly moderate the autism trait to suicide ideation relationship. Future work should explore this relationship longitudinally using objective measures before considering intervention work to increase sleep duration in those with elevated autism traits.

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8. Sampson KN, Upthegrove R, Abu-Akel A, Haque S, Wood SJ, Reniers R. Co-occurrence of autistic and psychotic traits : implications for depression, self-harm and suicidality. Psychol Med ;2020 (Feb 21):1-9.

BACKGROUND : There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality. METHODS : Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed. RESULTS : A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits. CONCLUSIONS : This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.

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