Environmental risk factors for autism: Do they help cause de novo genetic mutations that contribute to the disorder?

Abstract

Recent research has discovered that a number of genetic risk factors for autism are de novo mutations. Advanced parental age at the time of conception is associated with increased risk for both autism and de novo mutations. We investigated the hypothesis that other environmental factors associated with increased risk for autism might also be mutagenic and contribute to autism by causing de novo mutations. A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors – mercury, cadmium, nickel, trichloroethylene, and vinyl chloride – are established mutagens. Another four – including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation – are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress – a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA. We note how de novo mutations may also help explain why the concordance rate for autism is so markedly higher in monozygotic than dizygotic twins. De novo mutations may also explain in part why the prevalence of autism is so remarkably high, given the evidence for a strong role of genetic factors and the low fertility of individuals with autism – and resultant selection pressure against autism susceptibility genes. These several lines of evidence provide support for the hypothesis, and warrant new research approaches – which we suggest – to address limitations in existing studies. The hypothesis has implications for understanding possible etiologic roles of de novo mutations in autism, and it suggests possible approaches to primary prevention of the disorder, such as addressing widespread vitamin D deficiency and exposure to known mutagens.

Autism Spectrum Disorders and Communication Disorders: Influences of Advanced Parental Age and Use of Assisted Reproductive Technology

“…Additionally, studies have pointed out the genetic alterations that may be inherent to fertility issues, implicating a form of natural selection/genetic viability (e.g., Kong et al 2012). The effects of additional environmental factors on these heritable mutations are unclear (Kinney et al 2010;Kong et al 2012).…”

“…Overwhelmingly, researchers who have considered adverse outcomes of ART use, genetic influences, parental ages at the time of conception, environmental influences, and other risk factors for incidence of ASD agree that findings of their studies and/or others' are limited (Awadalla et al 2010;Hultman et al 2011;Julie et al 2011;Kinney et al 2010;Durkin et al 2010;Ponjaert-Kristoffersen et al 2005). Some findings are similar and others confounding.…”

Autism Spectrum Disorder (ASD); The Past, The Present, and The Future

“…), and neonatal complications (like respiratory distress syndrome, intracranial hemorrhage, indirect hyperbilirubinemic encephalopathy, etc.) [24][25][26][27][28][29][30]. interestingly, some autistic mothers have been proved to have antibodies against fetal brain proteins which cross the placenta and interfere with the development of fetal brain with subsequent development of ASD [31,32].…”

“…On the other hand, deficiency of vitamin D, which is an immunemodulator, strong antioxidant guarding against oxidative stress, and natural protector against mutations because of its DNA repair promoting features, has been found to be one of the potential causes of autism [27,[33][34][35].…”

L’autisme dans la presse spécialisée destinée aux travailleurs sociaux : évolution des discours, enjeux de pratique, de recherche et de formation

“…Concernant les facteurs environnementaux d' ordre biologique, des données convaincantes montrent que la prévalence de l'autisme est multipliée par cinq chez les enfants nés de mères en grave déficit de vitamine D : puisque la vitamine D est un cofacteur pour les enzymes qui réparent les erreurs de copie d' ADN, le déficit en vitamine D augmente le risque de mutation de novo. Des études ont également porté sur les effets à l' exposition au mercure et à des perturbations du système immunitaire (Currenti, 2010 ;Kinney, 2010). Concernant les facteurs environnementaux de type interaction sociales, la littérature biomédicale a démontré qu'une maltraitance sévère dans la petite enfance peut entraîner un syndrome autistique (Ruter & al., 2007).…”