Ruth Monk

Autism is a relatively common neurodevelopmental difference with considerable phenotypic heterogeneity impacting cognitive, sensory, and social processing, and often co‐occurs with other conditions. Therefore, there is not a one‐size‐fits‐all clinical support pathway for autistic individuals following diagnosis. DNA sequencing technology has enabled the discovery of genes causative of, or associated with, autism. Unsurprisingly, genetic heterogeneity goes hand‐in‐hand with the phenotypic heterogeneity for this condition; with causative genetic variation ranging from single base pair changes to complex chromosomal rearrangements in more than 100 different genes. This study captures a snapshot (201 individuals) of the autistic population (both clinically referred and self‐referred) in Aotearoa New Zealand and documents a decade's research effort to refine diagnosis using a flexible and customised genome‐wide sequencing approach. The diagnostic yield in this phenotypically disparate cohort was 12.9%, with an additional 15.9% of individuals harbouring ‘likely causal’ variants, providing the groundwork to tailor clinical, social, and educational care. Importantly, this study reveals the diagnostic utility of customised genetic screening for autism across a phenotypically diverse autistic population.

Over the past two decades, there have been increasing discussions around which terms should be used to talk about autism. Whilst these discussions have largely revolved around the suitability of identity‐first language and person‐first language, more recently this debate has broadened to encompass other autism‐related terminology (e.g., ‘high‐functioning’). To date, academic studies have not investigated the language preferences of autistic individuals outside of the United Kingdom or Australia, nor have they compared levels of endorsement across countries. Hence, the current study adopted a mixed‐methods approach, employing both quantitative and qualitative techniques, to explore the linguistic preferences of 654 English‐speaking autistic adults across the globe. Despite variation in levels of endorsement between countries, we found that the most popular terms were similar—the terms ‘Autism’, ‘Autistic person’, ‘Is autistic’, ‘Neurological/Brain Difference’, ‘Differences’, ‘Challenges’, ‘Difficulties’, ‘Neurotypical people’, and ‘Neurotypicals’ were consistently favored across countries. Despite relative consensus across groups, both our quantitative and qualitative data demonstrate that there is no universally accepted way to talk about autism. Our thematic analysis revealed the reasons underlying participants’ preferences, generating six core themes, and illuminated an important guiding principle—to respect personal preferences. These findings have significant implications for informing practice, research and language policy worldwide.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by the progressive loss of striatal medium spiny neurons. Using a highly efficient protocol for direct reprogramming of adult human fibroblasts with chemically modified mRNA, we report the first generation of HD induced neural precursor cells (iNPs) expressing striatal lineage markers that differentiated into DARPP32+ neurons from individuals with adult-onset HD (41-57 CAG). While no transcriptional differences between normal and HD reprogrammed neurons were detected by NanoString nCounter analysis, a subpopulation of HD reprogrammed neurons contained ubiquitinated polyglutamine aggregates. Importantly, reprogrammed HD neurons exhibited impaired neuronal maturation, displaying altered neurite morphology and more depolarized resting membrane potentials. Reduced BDNF protein expression in reprogrammed HD neurons correlated with increased CAG repeat lengths and earlier symptom onset. This model represents a platform for investigating impaired neuronal maturation and screening for neuronal maturation modifiers to treat HD.