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Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits.

ABSTRACT: Autism is a highly heritable, heterogeneous, neurodevelopmental condition. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex families and autistic traits still warrants investigation. Here, we conducted whole-genome sequencing of 21 highly multiplex autism families, with at least three autistic individuals in each family, to prioritise genes associated with autism. Using a combination of both autistic traits and clinical diagnosis of autism, we identify rare variants in genes associated with autism, and related neurodevelopmental conditions in multiple families. We identify a modest excess of these variants in autistic individuals compared to individuals without an autism diagnosis. Finally, we identify a convergence of the genes identified in molecular pathways related to development and neurogenesis. In sum, our analysis provides initial evidence to demonstrate the value of integrating autism diagnosis and autistic traits to prioritise genes.

SUBMITTER: More RP

PROVIDER: S-EPMC10575770 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits.

More Ravi Prabhakar RP Warrier Varun V Brunel Helena H Buckingham Clara C Smith Paula P Allison Carrie C Holt Rosemary R Bradshaw Charles R CR Baron-Cohen Simon S

Molecular psychiatry 20230126 5

Autism is a highly heritable, heterogeneous, neurodevelopmental condition. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex families and autistic traits still warrants investigation. Here, we conducted whole-genome sequencing of 21 highly multiplex autism families, with at least three autistic individuals in each family, t ...[more]

PMID: 36702863

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Project description:There has been limited research on families of autistic children in Ecuador, especially in relation to their experiences of accessing a diagnosis and associated support. In this study, we surveyed 767 families about their diagnostic and post-diagnostic journeys. Of these, 651 families had children who had received a formal autism diagnosis. In this group, we found that families usually suspected that their children may be developing atypically when they were between 6 and 48 months of age; families typically consulted a professional shortly after noticing signs of atypical development (e.g. within 6 months); most children received a diagnosis before the age of 48 months; and families typically reported consulting four or more different professionals to attain a diagnosis for their children. Families' feelings and thoughts related to the diagnostic and post-diagnostic journey were often negative and were underpinned by concerns around a lack of information and services. We conclude with recommendations for optimal diagnostic and post-diagnostic support for autistic children and their families in Ecuador.Lay abstractThere has been much research about the experiences of families of autistic children as they navigate the process of accessing a diagnosis and associated support. However, most of this work has been conducted in Europe, the United States, and Australia. In this study, we examined the experiences of 767 families in Ecuador via an in-depth survey. Of the families we surveyed, 651 had children whose journeys resulted in them receiving a formal autism diagnosis. Most families realized that their children might have developmental differences when they were between the ages of 6 and 48 months, after which they tended to seek support from a professional fairly quickly (i.e. within 6 months). Most families consulted with several different professionals before they accessed a diagnosis for their children, with children tending to receive a diagnosis before the age of 48 months. Families often reported negative emotions around their children's diagnostic and post-diagnostic journeys, which were commonly related to the lack of information and services available to them. We hope that through gaining a greater understanding of the experiences of families of autistic children in Ecuador, these findings can be used to inform public policies that lead to the development of supports and services that better meet the needs of autistic people and their families in this context.

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Dataset Information

Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits.

Publications

Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits.

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