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.

自闭症是一类较为常见的神经发育异质性疾病，存在显著的表型异质性，可对认知、感知与社会信息加工过程造成影响，且常与其他病症共病。因此，自闭症患者确诊后，并无适用于所有个体的统一临床支持路径。DNA测序技术（DNA sequencing technology）已助力科研人员发现与自闭症致病相关或存在关联的基因。不出所料，该病症的遗传异质性与表型异质性紧密关联；致病遗传变异的类型跨度极大，从单碱基替换（single base pair changes）到复杂染色体重排（complex chromosomal rearrangements），涉及超过100个不同基因。本研究对新西兰（Aotearoa）的自闭症人群（涵盖临床转诊与自我转诊两类个体）开展了抽样调查，共纳入201名受试者，并记录了十年来采用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历程。在这一表型异质性显著的队列中，诊断检出率为12.9%，另有15.9%的个体携带“疑似致病”变异，该成果为定制化临床、社会及教育照护方案奠定了坚实基础。尤为重要的是，本研究证实了定制化基因筛查在表型多样的自闭症人群中用于自闭症诊断的应用价值。