1. Bacchelli E, Loi E, Cameli C, Moi L, Benedetti AFV, Blois S, Fadda A, Bonora E, Mattu S, Fadda R, Chessa R, Maestrini E, Doneddu G, Zavattari P. {{Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies CAPG as a Functionally Relevant Candidate Gene}}. {J Clin Med}. 2019; 8(2).
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with high heritability, although their underlying genetic factors are still largely unknown. Here we present a comprehensive genetic characterization of two ASD siblings from Sardinia by genome-wide copy number variation analysis and whole exome sequencing (WES), to identify novel genetic alterations associated with this disorder. Single nucleotide polymorphism (SNP) array data revealed a rare microdeletion involving CAPG, ELMOD3, and SH2D6 genes, in both siblings. CAPG encodes for a postsynaptic density (PSD) protein known to regulate spine morphogenesis and synaptic formation. The reduced CAPG mRNA and protein expression levels in ASD patients, in the presence of hemizygosity or a particular genetic and/or epigenetic background, highlighted the functional relevance of CAPG as a candidate gene for ASD. WES analysis led to the identification in both affected siblings of a rare frameshift mutation in VDAC3, a gene intolerant to loss of function mutation, encoding for a voltage-dependent anion channel localized on PSD. Moreover, four missense damaging variants were identified in genes intolerant to loss of function variation encoding for PSD proteins: PLXNA2, KCTD16, ARHGAP21, and SLC4A1. This study identifies CAPG and VDAC3 as candidate genes and provides additional support for genes encoding PSD proteins in ASD susceptibility.
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2. Hohn VD, de Veld DMJ, Mataw KJS, van Someren EJW, Begeer S. {{Insomnia Severity in Adults with Autism Spectrum Disorder is Associated with sensory Hyper-Reactivity and Social Skill Impairment}}. {J Autism Dev Disord}. 2019.
Insomnia is a common source of distress in adults with autism spectrum disorder (ASD). Two characteristics of ASD could be relevant to insomnia complaints by hampering the entrainment of a circadian sleep-wake rhythm. First, sensory hyper-reactivity could lead to bright light avoidance and thus affect photoperiodic input to the circadian system. Second, impaired social skills complicate the establishment of a social interactions and thus affect scheduled social-behavioral input to the circadian system. We investigated the association of insomnia severity with sensory reactivity and social skills in 631 adults (18-65 years) with ASD. Results revealed positive associations of insomnia severity with general and visual sensory hyper-reactivity and with impairment of social skills. The findings warrant further studies which (1) directly assess whether a suboptimal functioning of the biological clock underlies these associations and (2) identify other factors that could contribute to observed sleep problems.
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3. Mirkovic B, Gerardin P. {{Asperger’s syndrome: What to consider?}}. {L’Encephale}. 2019.
Asperger’s syndrome is a neurodevelopmental disorder which is part of the large family of autism spectrum disorders. People with Asperger’s syndrome have difficulties in social interactions, verbal and non-verbal communication, and may display behavioural oddities, with stereotypies and limited interests. They show no language delay and their cognitive development is not marked by an overall delay but by specific impairments in certain areas such as the executive functions. The clinical presentations are very heterogeneous, varying according to age and psychiatric comorbidities. Screening, diagnosis and specialized treatment are not made any easier by the diversity of the clinical manifestations. Asperger’s syndrome is often diagnosed belatedly, at 11years of age on average and even in adulthood in some cases. This late diagnosis has a significant impact on the risks of depression and a poor quality of life. However, in adulthood or in adolescence, certain situations, personality traits and cognitive profiles or certain comorbidities should suggest the hypothesis of an Asperger-type autism spectrum disorder. We propose here a review of the clinical situations at different ages of life that could help with the screening and the referral of patients to specialized clinicians for diagnosis and appropriate treatment.
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4. Rosman NP. {{Childhood disintegrative disorder: part of the autism spectrum?}}. {Dev Med Child Neurol}. 2019.
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5. He X, Zhao P, Huang Y, Cai X, Bi B, Lin J. {{[Genome-wide copy number microarray analysis for a boy with autism]}}. {Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics}. 2019; 36(2): 157-60.
OBJECTIVE: To carry out genome-wide copy number variations (CNVs) analysis for a boy with autism by using single nucleotide polymorphism array (SNP array). METHODS: SNP array analysis was conducted for the boy and his parents, and the data was validated by real-time PCR. Correlation between the deleted genes and the phenotype was analyzed by reviewing the literature. RESULTS: The patient was found to carry a terminal deletion of 18q22.3q23 (7.1 Mb), which involved FBXO15, ZNF407, ZADH2, TSHZ1, MBP and ADNP2 genes. No pathogenic CNVs were found in the parents. Comparison of the patient with cases reported in the literature suggested that the ZNF407 gene probably accounts for the autistic phenotype in these patients. CONCLUSION: The autistic phenotype of the patient may be attributed to the 18q deletion, for which ZNF407 may be a critical candidate. SNP array has provided an useful tool for the study of molecular mechanism underlying autism.
