Gene-environment interactions in Autism Spectrum Disorders (ASD)

Spectrum Disorder (ASD), is a heterogeneous neurodevelopmental disorder with na estimated global prevalence rate of 17:10000, and a male to female ratio of 4:1. Patients with ASD presente language and communication difficulties and stereotyped behaviours. Comorbidity with other disorders, such as Intelectual Disability, Fragile-X syndrome (FXS) epilepsy and tuberous sclerosis frequently occurs. ASD presents amultifactorial etiopathology, and genetic factos alone are not suficiente to explain how the syndrome arises, with recente studies establishing ASD heritability at approximately 50%. Pre-, peri- and post-natal exposure to toxic environmental factos has been implicated in the development of ASD. Involvement of epigenetic regulatory mechanisms has been suggested, supported by the occurrence of autistic symptoms in patients with disorders aris ing from epigenetic mutations, such as FXS. A polygenic and epistatic model is a strong hypothesis to explain ASD. The main goal of this project is to identify specific exposure patterns to environmental toxicants in children diagnosed with ASD and integrate the results with genetic and epigenetic data.

Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Introduction: Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk 1, and are associated with specific phenotypic manifestations 2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described 3, 4. An increased prevalence of autism - like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP) 5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS) 6 and Broad Autism Phenotype Questionnaire (BAPQ) 7 reports . The SRS is 65 - item questionnaire to identify sub - clinical social impairments and interpersonal behaviour in individuals . The BAPQ is a 36 - item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk1, and are associated with specific phenotypic manifestations2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described3,4. An increased prevalence of autism-like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP)5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS)6 and Broad Autism Phenotype Questionnaire (BAPQ)7 reports. The SRS is 65-item questionnaire to identify sub-clinical social impairments and interpersonal behaviour in individuals. The BAPQ is a 36-item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Rastreio neonatal dos défices do ciclo da ureia em Portugal

Os défices do ciclo da ureia são um grupo de doenças hereditárias do metabolismo caracterizadas fundamentalmente por uma acumulação de amónia. Clinicamente o espectro é muito alargado, com formas de apresentação no período neonatal até situações mais moderadas de apresentação tardia em adultos. O tratamento é fundamentalmente de base nutricional e traduz-se numa redução significativa da mortalidade e morbilidade. Com a introdução da espectrometria de massa nos laboratórios de rastreio neonatal em meados dos anos 90, passou a ser possível quantificar alguns intermediários do ciclo, o que associado à existência de um intervalo livre e um tratamento eficaz, permitiu o rastreio de algumas das doenças deste grupo. Em 2004 iniciou-se em Portugal o rastreio dos défices do ciclo da ureia, tendo-se rastreado até ao presente, 988 687 recém-nascidos e identificado 19 casos positivos. Recentes desenvolvimentos técnicos vieram possibilitar a quantificação de novos marcadores, mais concretamente do ácido orótico, o que abre a possibilidade de rastrear o défice em ornitina transcarbamilase, o défice do ciclo da ureia mais frequente. Os autores apresentam a situação atual do rastreio dos défices do ciclo da ureia e as perspetivas em virtude dos novos desenvolvimentos técnicos.