Genetic diagnostic outcomes from a 10-year research programme in autism in Aotearoa New Zealand

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（Autism）是一种较为常见的神经发育差异，具有显著的表型异质性，可影响认知、感知与社会信息加工过程，且常与其他病症共现。因此，确诊后的自闭症个体并无通用统一的临床支持路径。DNA测序（DNA sequencing）技术已助力发现与自闭症致病或相关的基因。不出所料，该病症的遗传异质性与表型异质性密切相关；致病遗传变异类型多样，覆盖单碱基替换至复杂染色体重排，涉及超过100种不同基因。本研究对新西兰（Aotearoa New Zealand）的自闭症人群（涵盖临床转诊与自我转诊两类个体）进行了抽样调研（共201名受试者），并记录了十年来通过灵活定制化全基因组测序（genome-wide sequencing）技术优化自闭症诊断的研究工作。该表型异质性队列的诊断检出率为12.9%，另有15.9%的个体携带"疑似致病"变异，为定制化的临床、社会与教育照护方案奠定了基础。尤为重要的是，本研究证实了定制化自闭症遗传筛查在表型多样的自闭症人群中的诊断应用价值。