Autismo y epigenética. Un modelo de explicación para la comprensión de la génesis en los trastornos del espectro autista / [Autism and epigenetics. A model of explanation for the understanding of the genesis in autism spectrum disorders].

Autism spectrum disorders are characterized by impairment of social integration and language development and restricted interests. Autism spectrum disorders manifest during childhood and may have a varying clinical expression over the years related to different therapeutic approaches, behavior-modifying drugs, and environmental factors, among others. So far, the genetic alterations identified are not sufficient to explain the genesis of all these processes, as many of the mutations found are also present in unaffected individuals. Findings on the underlying biological and pathophysiological mechanisms of entities strongly associated with autism spectrum disorders, such as Rett, fragile X, Angelman, and fetal alcohol syndromes, point to the role of epigenetic changes in disorders of neurodevelopment. Epigenetic phenomena are normal biological processes necessary for cell and thus human life, especially related to embryonic development. Different phenomena that affect epigenetic processes (changes that change operation or expression of a gene, without modifying the DNA structure) have also been shown to be important in the genesis of neurodevelopmental disorders. Alterations in the epigenetic mechanism may be reversible, which may explain the variation in the autism phenotype over time. Here we analyze the normal epigenetic mechanisms, autism spectrum disorders, their association with specific entities associated with altered epigenetic mechanisms, and possible therapeutic approaches targeting these alterations.

Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en la población antioqueña / Evidence for association and epistasis between the genetic markers SLC6A4 and HTR2A in autism etiology

Introducción. El espectro autista constituye un grupo de trastornos graves del neurodesarrollo, con un fuerte componente genético. Se ha sugerido un papel importante del sistema serotoninérgico en el desarrollo de este grupo de trastornos, con base en los estudios de respuesta a medicamentos y la hiperserotoninemia, característica común en el autismo. Se han implicado múltiples moléculas en el metabolismo y la neurotransmisión de la serotonina; sin embargo, los resultados de los estudios han tenido poca congruencia entre diferentes poblaciones. Objetivos. Evaluar la relación entre el autismo y el polimorfismo de nucleótido simple (Single Nucleotide Polymorphism, SNP) en los genes SLC6A4, HTR2A e ITGB3, en una muestra de la población antioqueña. Materiales y métodos. Se genotipificaron 42 núcleos familiares con autismo para 10 variantes en los genes SLC6A4, ITGB3 y HTR2A. Se evaluó la asociación utilizando la prueba de desequilibrio en la transmisión. Se exploró el impacto de la interacción entre estos genes y el autismo, utilizando la reducción multidimensional. Resultados. Se encontró asociación de las variantes rs4583306 (OR=2,6, p=0,004) y rs2066713 (OR=2,2 p=0,03), en el gen SLC6A4, y asociación de combinaciones genotípicas entre los genes SLC6A4 y HTR2A y el riesgo de autismo (p=0,0001). Conclusiones. Se encontró asociación significativa con variantes en el gen transportador de serotonina con el autismo, al igual que interacción entre variantes en los genes HTR2A con SLC6A4. Estos resultados concuerdan con los de estudios previos en otras poblaciones y son pruebas a favor del papel del sistema serotoninérgico en la etiología del espectro autista.

Introduction. Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations. Objectives. The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia. Materials and methods. In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods. Results. A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001). Conclusion. Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Autism and parents' education. New data from the developing world

To investigate the link between autism disorders and engineering training of parents. All Autistic-Pervasive Developmental Disorders [PDD] children that were diagnosed on the bases of the Diagnostic and Statistical Manual for Mental Disorders [DSM-IV], and met the required criteria for autism, over a defined period [March 2006 to June 2007] were included. We then took all non-PDD developmental disorders cases seen during the same time frame as the autistic children as a control; these included speech delay, mental retardation, and down's syndrome. Out data covered demographic data, parents and grandparents' education, and profession. Parents' education/professions were classified into 2 groups only, 1- engineering or mathematician; and 2-humanities, neither engineering nor math. The children were divided into 2 groups, autism [57 cases], and developmental disorders [40 cases]. Regarding the main question of this study [hypothesized engineering link], the data showed some differences between the 2 groups [x[2]=2.503, degrees of freedom[df]=1; p=0.093], but not of major significance. There was no significant difference [x[2]0.370; df=2; p=0.831] between the 2 groups on the variable of consanguinity. We have found that the Saudi Arabian sample, though relatively small, has considerable similarities with both the UK and USA data. There is a possibility of an association between autism and the engineering/math training of fathers. The implication is briefly discussed

Genetic studies in children with intellectual disability and autistic spectrum of disorders.

Autism is one of the five disorders that falls under the umbrella of Pervasive Developmental Disorders (PDD) or Autism Spectrum Disorder (ASD), a category of neurological disorders characterized by “severe and pervasive impairment in several areas of development.” ASD is characterized by varying degrees of impairment in communication skills, social interaction and restricted, repetitive stereotyped patterns of behavior. The five disorders under PDD are autistic disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder and PDD-not otherwise specified. ASD can often be reliably detected by the age of 3 years and, in some cases, as early as 18 months. The appearance of any warning signs of ASD is reason to have the child evaluated by a professional specializing in these disorders.

Aspectos explicativos de comorbilidad en los TGD, el síndrome de Asperger y el TDAH: estado de la cuestión / Explanatory aspects of comorbidity in PDD, Asperger syndrome and ADHD: the current state

El presente artículo revisa la evidencia científica reciente sobre los aspectos comórbidos de los Trastornos Generalizados del Desarrollo (TGD), especialmente los tipos de alto funcionamiento, y el Trastorno por Déficit de Atención con Hiperactividad (TDAH). Se comentan varios estudios desde diferentes perspectivas (epidemiología, investigación neurocognitiva y genética). Finalmente, las áreas investigadas coinciden en la necesidad de reformular los criterios diagnósticos del DSM-IV y la CIE-10 en futuras clasificaciones de los TGD.

The present article reviews the recent scientific evidence about the comorbid aspects of Pervasive Developmental Disorders (PDD), especially high-functioning types, and Attention-Deficit Hyperactivity Disorder (ADHD). Several studies from different perspectives (epidemiology, neurocognitive research and genetics) are discussed. Finally, the investigated areas coincide with the need to reformulate the DSM-IV and the ICD-10 diagnostic criteria in future classifications of PDD.

Subtelomeric region of chromosome 2 in patients with autism spectrum disorders

Autism spectrum disorders are severe psychiatric diseases commonly identified in the population. They are diagnosed during childhood and the etiology has been much debated due to their variations and complexity. Onset is early and characterized as communication and social interaction disorders and as repetitive and stereotyped behavior. Austistic disorders may occur together with various genetic and chromosomal diseases. Several chromosomal regions and genes are implicated in the predisposition for these diseases, in particular those with products expressed in the central nervous system. There are reports of autistic and mentally handicapped patients with submicroscopic subtelomeric alterations at the distal end of the long arm of chromosome 2. Additionally, there is evidence that alterations at 2q37 cause brain malformations that result in the autistic phenotype. These alterations are very small and not identified by routine cytogenetics to which patients are normally submitted, which may result in an underestimation of the diagnosis. This study aimed at evaluating the 2q37 region in patients with autistic disorders. Twenty patients were studied utilizing the fluorescence in situ hybridization technique with a specific probe for 2q37. All of them were also studied by the GTC banding technique to identify possible chromosomal diseases. No alterations were observed in the 2q37 region of the individuals studied, and no patient presented chromosomal diseases. This result may be due to the small sample size analyzed. The introduction of routine analysis of the 2q37 region for patients with autistic disorders depends on further studies.

A case of pervasive developmental disorder with chromosomal translocation 1-4

A 5-year-old girl is described as pervasive developmental disorder associated to chromosome 1-4 translocation, being such association not described till this moment in specialized literature.

Descrevemos uma menina de 5 anos de idade portadora de transtorno invasivo do desenvolvimento associado a translocação dos cromossomos 1-4, associação essa não descrita na literatura especializada até o presente momento.