Investigation of de-novo copy number variants in patients with Autism Spectrum Disorder in Vietnam

Bui, H 2021, Investigation of de-novo copy number variants in patients with Autism Spectrum Disorder in Vietnam , PhD thesis, University of Salford.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a prevalence of approximately 1% children worldwide. ASD is characterized by deficits in social communication and interaction and the presence of restricted interests and repetitive behaviours. Genetic alterations contributing to increasing risk of ASD have been reported. Early genetic screening, especially for families with a positive ASD history, could aid the early diagnosis and potentially more effective disease management strategies. Copy number variants (CNVs) are the alterations in the structure of chromosome and reported as a significant contribution to the pathogenesis of ASD. Currently, genome-wide DNA microarray (e.g. microarray comparative genomic hybridization (aCGH)) is considered as the first-tier screen for genetic aberrations in autistic children, albeit with a limited success (around 10% in studies primarily based on patients of Caucasian origin). Currently, there is no comprehensive study on the diagnostic potential of aCGH in autistic children from Vietnam. This study aims to investigate the possible role of CNV in Vietnamese patients with a clinical diagnosis of ASD. One hundred trios (both parents and at least one child) were recruited where in each trio the child was clinically diagnosed with ASD while the parents were not clinically affected. MECP2 and FMR1 DNA tests were performed for excluding Rett Syndrome and Fragile X syndrome as possible causes, respectively. The aCGH test was performed on all patients as well as their parents to identify de-novo CNVs in the patients. We detected 442 non-redundant CNVs in 100 patients with 210 (47.5%) identified as de novo in origin. We identified five variants of uncertain significance (VUS) as well as pathogenic de novo CNVs (two duplication and three deletion CNVs) in seven patients (four males and three females) related to autism based on the SFARI (Simons Foundation Autism Research Initiative) database. In six patients, four known pathogenic CNVs were identified (diagnostic success 6%). We found the highest (3%) contribution of deletions involving SHANK3 gene, which could pave the way for future diagnostics focused on this gene alone. These findings provide initial information for building an aCGH screening test for Vietnamese autistic children and identifying the relationship between genetic alterations and the effectiveness of stem cell transplantation – bringing a new strategy for ASD management in Vietnam.

Item Type: Thesis (PhD)
Contributors: Mukhopadhyay, A (Supervisor), Goodhead, IB (Supervisor) and Nguyen, LT (Supervisor)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Funders: Vinmec Healthcare system, Vietnam
Depositing User: Hoa Bui
Date Deposited: 09 Nov 2021 14:21
Last Modified: 15 Feb 2022 14:47

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