Parents' perspectives on conversations about prognosis and an assessment of prognostic information available online: A mixed-methods study.

Background: Conversations about prognosis for genetic neurodevelopmental conditions are becoming more frequent; however, there is a lack of evidence and guidance on how to approach these conversations and frame the information being provided.

Objective: (1) To understand how parents perceive prognostic conversations with healthcare professionals and their preferences for these conversations, (2) To investigate the framing of prognostic information found online.

Methods: This was a mixed-methods study, comprising of (1) a thematic analysis of interviews with parents and (2) a quantification of prognostic information available on the internet that portrayed a negative message.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

Aim: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue.

Topoisomerase I inhibition leads to length-dependent gene expression changes in human primary astrocytes.

Topoisomerase I is required for the proper expression of long genes (> 100 kb) in mouse and human cortical neurons, including many candidate genes for autism spectrum disorder (ASD) [1]. Given the important role of astrocytes in brain development [2], we investigated whether long genes, including autism susceptibility genes, also require topoisomerase I expression in human primary astrocytes. We carried genome-wide expression profiling of cultured human primary astrocytes following treatment with the topoisomerase I inhibitor Topotecan, using Illumina microarrays.

Transcriptional response to mitochondrial protease IMMP2L knockdown in human primary astrocytes.

IMMP2L encodes the inner membrane peptidase subunit 2, a mitochondrial protease involved in cleaving the space-sorting signals of mitochondrial membrane proteins. IMMP2L has been implicated in Tourette syndrome, but how its dysfunction contributes to the neurodevelopmental phenotype remains unclear. Here we show that IMMP2L transcription requires Topoisomerase I in human primary astrocytes, and characterize the downstream effects of IMMP2L knockdown on gene expression.

Searching for convergent pathways in autism spectrum disorders: insights from human brain transcriptome studies.

Autism spectrum disorder (ASD) is one of the most heritable neuropsychiatric conditions. The complex genetic landscape of the disorder includes both common and rare variants at hundreds of genetic loci. This marked heterogeneity has thus far hampered efforts to develop genetic diagnostic panels and targeted pharmacological therapies.

Coexpression networks identify brain region-specific enhancer RNAs in the human brain.

Despite major progress in identifying enhancer regions on a genome-wide scale, the majority of available data are limited to model organisms and human transformed cell lines. We have identified a robust set of enhancer RNAs (eRNAs) expressed in the human brain and constructed networks assessing eRNA-gene coexpression interactions across human fetal brain and multiple adult brain regions. Our data identify brain region-specific eRNAs and show that enhancer regions expressing eRNAs are enriched for genetic variants associated with autism spectrum disorders.