scholarly journals Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations

2021 ◽  
pp. 070674372110414
Author(s):  
Pierre Defresne ◽  
Laurent Mottron
Keyword(s):  
Autism Spectrum Disorder ◽  
Clinical Practice ◽  
Diagnostic Criteria ◽  
Genetic Variants ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Clinical Expression ◽  
Broad Category ◽  
Diagnostic Instruments ◽  
Common Genetic Variants

The “autism spectrum disorder” (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.

scholarly journals Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

2016 ◽  
Vol 10 ◽  
Author(s):  
Anthony R. Torres ◽  
Thayne L. Sweeten ◽  
Randall C. Johnson ◽  
Dennis Odell ◽  
Jonna B. Westover ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Genetic Variants ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Immune Genes ◽  
Common Genetic Variants

scholarly journals Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidekazu Kato ◽  
Itaru Kushima ◽  
Daisuke Mori ◽  
Akira Yoshimi ◽  
Branko Aleksic ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Histone Methylation ◽  
Genetic Variants ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Gene Encoding ◽  
Rare Genetic Variants ◽  
Lysine Demethylase ◽  
Methylation Patterns ◽  
Sample Set

AbstractDysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

scholarly journals Genomics of autism spectrum disorder: approach to therapy

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 627 ◽  
Author(s):  
Fatma Ayhan ◽  
Genevieve Konopka
Keyword(s):  
Autism Spectrum Disorder ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Protein Translation ◽  
Autism Spectrum ◽  
Current Treatment ◽  
Spectrum Disorder ◽  
Current State ◽  
Genetics And Genomics

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition with no current treatment available. Although advances in genetics and genomics have identified hundreds of genes associated with ASD, very little is known about the pathophysiology of ASD and the functional contribution of specific genes to ASD phenotypes. Improved understanding of the biological function of ASD-associated genes and how this heterogeneous group of genetic variants leads to the disease is needed in order to develop therapeutic strategies. Here, we review the current state of ASD research related to gene discovery and examples of emerging molecular mechanisms (protein translation and alternative splicing). In addition, we discuss how patient-derived three-dimensional brain organoids might provide an opportunity to model specific genetic variants in order to define molecular and cellular defects that could be amenable for developing and screening personalized therapies related to ASD.

scholarly journals Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort

2019 ◽  
Vol 215 (5) ◽  
pp. 647-653 ◽  
Author(s):  
Jack F. G. Underwood ◽  
Kimberley M. Kendall ◽  
Jennifer Berrett ◽  
Catrin Lewis ◽  
Richard Anney ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social History ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Self Report ◽  
Risk Scores ◽  
Rare Cnvs ◽  
Patient Counselling ◽  
Genetic Characteristics ◽  
Common Genetic Variants

BackgroundThe past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients.AimsThis e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services.MethodIndividuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated.ResultsOf individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs.ConclusionsThis study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD.Declaration of interestNone.

Diagnostic instruments for autism spectrum disorder (ASD)

2016 ◽  
Author(s):  
Leonora Vllasaliu ◽  
Katrin Jensen ◽  
Stephanie Hoss ◽  
Marie Landenberger ◽  
Marianne Menze ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Diagnostic Instruments
Sign in / Sign up

Export Citation Format

Share Document