Diagnostic outcome and novel gene discovery of whole exome sequencing in Hong Kong families with autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder causing significant disease burden. Common genetic variations explain the majority of ASD cases yet a significant proportion of ASD subjects have a monogenic cause. Achieving a molecular diagnosis not only allows more accurate prognostication and genetic counselling of recurrence risk, but also has important implications on management. This dissertation aimed to apply exome sequencing (ES) to study the diagnostic yield and mutational spectrum of ASD subjects in Hong Kong. A positive molecular diagnosis could be found in 5.3% of subjects and a diverse spectrum of mutations was observed. Through international collaboration, GNB2 was identified as a novel disease gene causing neurodevelopmental disorder. This study demonstrated ES as an effective diagnostic test in ASD. The identification of novel ASD gene candidates also highlight the potential of diagnostic ES data in novel gene discovery.