Musgrave Suzanne M, Taylor Juliet, Whitford Whitney, Garton Alexandra, Poquérusse Jessie, Hawkins Victoria, Port Waiora, Moodley Kriebashne S, Monk Ruth, Knowles Sarah D, Walker Caroline, Samson Christopher, Velzian Lydia, Swan Brendan, Love Donald R, Hill Rosamund, Muir Colette, Talkowski Michael E, Lowther Chelsea, Snell Russell G, Lehnert Klaus, Jacobsen Jessie C
School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
J R Soc N Z. 2024 Sep 18;55(6):2464-2480. doi: 10.1080/03036758.2024.2394128. eCollection 2025.
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.
自闭症是一种相对常见的神经发育差异，具有显著的表型异质性，影响认知、感官和社交处理，且常与其他病症并发。因此，自闭症患者确诊后并没有适用于所有人的临床支持路径。DNA测序技术已使引发自闭症或与之相关的基因得以发现。不出所料，这种病症的遗传异质性与表型异质性并存；致病基因变异范围从单碱基对变化到100多个不同基因中的复杂染色体重排。本研究采集了新西兰奥特亚罗瓦自闭症群体（包括临床转诊和自我转诊）的一个样本（201人），记录了十年来使用灵活且定制化的全基因组测序方法优化诊断的研究工作。在这个表型各异的队列中，诊断率为12.9%，另有15.9%的个体携带“可能致病”变异，为量身定制临床、社会和教育护理奠定了基础。重要的是，本研究揭示了针对表型多样的自闭症群体进行定制化基因筛查对自闭症诊断的效用。
