1. Bianucci R, Perciaccante A, Lippi D, Charlier P, Appenzeller O. {{Did Blaise Pascal have autism spectrum disorder and a genetic predisposition for skull deformities?}}. {Med Hypotheses};2019 (Jan);122:180-183.
Many world-renowned scientists and artists had autism spectrum disorder (ASD). We suggest that the French mathematician and physicist Blaise Pascal (1623-1662) also had ASD. As a boy, he demonstrated his mastery of language, mathematics and science. He showed single-mindedness and obsessive interests in the pursuit of science in his younger years and later he pursued with religion with the same determination. Pascal neglected social interactions; he was cold and aloof and had an obsessive revulsion to any expression of emotional attachment. As shown by his funerary mask and the autopsy report Pascal had craniosynostosis (primary nonsyndromic oxycephaly) with atrophy of the right half of the face. Congenital facial asymmetry due to craniosynostosis has a genetic basis. This suggests that Pascal’s facial deformity may betray his propensity to suffer from genetically determined diseases including ASD. Despite the intrinsic limitations of a diagnosis based only on biographical information, we surmise that Pascal had the three key symptoms (obsessive interests, difficulty in social relationship and problems in communicating) that characterize ASD individuals.
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2. Francis SM, Camchong J, Brickman L, Goelkel-Garcia L, Mueller BA, Tseng A, Lim KO, Jacob S. {{Hypoconnectivity of insular resting-state networks in adolescents with Autism Spectrum Disorder}}. {Psychiatry Res Neuroimaging};2018 (Dec 7);283:104-112.
Autism Spectrum Disorder (ASD) is characterized by deficits in social interaction and communication. The anterior insula (AI) participates in emotional salience detection; and the posterior insula (PI) participates in sensorimotor integration and response selection. Meta-analyses have noted insula-based aberrant connectivity within ASD. Given the observed social impairments in ASD and the role of the insula in social information processing (SIP), investigating functional organization of this structure in ASD is important. We investigated differences in resting-state functional connectivity (RSFC) using fMRI in male youths with (N=13; mean=14.6 years; range: 10.2-18.0 years) and without ASD (N=17; mean=14.5 years; range: 10.0-17.5 years). With seed-based FC measures, we compared RSFC in insular networks. Hypoconnectivity was observed in ASD (AI-superior frontal gyrus (SFG); AI-thalamus; PI-inferior parietal lobule (IPL); PI-fusiform gyrus (FG); PI-lentiform nucleus/putamen). Using the Social Communication Questionnaire (SCQ) to assess social functioning, regression analyses yielded negative correlations between SCQ scores and RSFC (AI-SFG; AI-thalamus; PI-FG; PI-IPL). Given the insula’s connections to limbic regions, and its role in integrating external sensory stimuli with internal states, atypical activity in this structure may be associated with social deficits characterizing ASD. Our results suggest further investigation of the insula’s role in SIP across a continuum of social abilities is needed.
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3. Lebrun N, Mehler-Jacob C, Poirier K, Zordan C, Lacombe D, Carion N, Billuart P, Bienvenu T. {{Novel KDM5B splice variants identified in patients with developmental disorders: Functional consequences}}. {Gene};2018 (Dec 30);679:305-313.
Histone lysine methylation influences processes such as gene expression and DNA repair. Thirty Jumonji C (JmjC) domain-containing proteins have been identified and phylogenetically clustered into seven subfamilies. Most JmjC domain-containing proteins have been shown to possess histone demethylase activity toward specific histone methylation marks. One of these subfamilies, the KDM5 family, is characterized by five conserved domains and includes four members. Interestingly, de novo loss-of-function and missense variants in KDM5B were identified in patients with intellectual disability (ID) and autism spectrum disorder (ASD) but also in unaffected individuals. Here, we report two novel de novo splice variants in the KDM5B gene in three patients with ID and ASD. The c.808+1G>A variant was identified in a boy with mild ID and autism traits and is associated with a significant reduced KDM5B mRNA expression without alteration of its H3K4me3 pattern. In contrast, the c.576+2T>C variant was found in twins with global delay in developmental milestones, poor language and ASD. This variant causes the production of an abnormal transcript which may produce an altered protein with the loss of the ARID1B domain with an increase in global gene H3K4me3. Our data reinforces the recent observation that the KDM5B haploinsufficiency is not a mechanism involved in intellectual disability and that KDM5B disorder associated with LOF variants is a recessive disorder. However, some variants may also cause gain of function, and need to be interpreted with caution, and functional studies should be performed to identify the molecular consequences of these different rare variants.
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4. Li YM, Shen YD, Li YJ, Xun GL, Liu H, Wu RR, Xia K, Zhao JP, Ou JJ. {{Maternal dietary patterns, supplements intake and autism spectrum disorders: A preliminary case-control study}}. {Medicine (Baltimore)};2018 (Dec);97(52):e13902.
The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.
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5. Steinman G. {{IGF – Autism prevention/amelioration}}. {Med Hypotheses};2019 (Jan);122:45-47.
Autism continues to be a significant cause of psychosocial pathology in affected children and adults. Until recently, the predominant research thrust to uncover the cause of this condition has been the search for a major nuclear mutation. Although a small percentage of cases do demonstrate such a DNA fault, recent effort has come to emphasize problems in the biochemistry of its sufferers. In particular, insulin-like growth factor-1 (IGF) has become the center of concern in many laboratories. A deficiency in this growth factor, leading to insufficient neuron myelination and defective synapse function, appears to result in brain dysconnectivity during the first year of postpartum life, and cause social malfunction in childhood years and beyond. At least three approaches have been reported by which this deficiency can be corrected in neonates before irreversible damage has been caused. The overall purpose of this report is to bring together related observations and to evolve a coherent, plausible explanation of the cause and prevention of autism.
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6. Steinman G. {{Prenatal identification of autism propensity}}. {Med Hypotheses};2019 (Jan);122:210-211.
The innovative method described involves antepartum testing to determine if the fetus has the potential of later developing autism. A technique is detailed which allows examining the maternal blood for SNPs (single-nucleotide polymorphisms) known to be associated with IGF1/IRS1 cellular pathway malfunction potentially leading to brain dysconnectivity in neonates. Results can then be corroborated with umbilical cord sampling at birth by the Autism Index test. [The discussion presented here is the follow-up to the recent prior report: Steinman, G. IGF – Autism prevention/amelioration, Medical Hypotheses 2019;122:45-47].
