Abstract：
Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene-disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.
摘要：
无法解释的全球发育迟缓（GDD）和智力障碍（ID）共同影响了近2％的儿科人群。建立病因诊断对于疾病管理至关重要，预后评估，并为患者和家属提供身体和心理支持。基因组测序的进步允许基因-疾病关联的快速积累，并加速了对无法解释的GDD/ID的病因诊断的搜索。我们回顾了利用全基因组分析技术的最新研究，我们讨论了它们的诊断结果，优势,和限制。总的来说,外显子组测序(ES)和基因组测序(GS)优于染色体微阵列和靶向组测序.GS为ES和染色体微阵列区域提供覆盖，提供最大的诊断潜力，而ES和再分析ES阴性结果的成本目前仍低于仅GS的成本。因此,与分阶段方法或单独使用GS相比，单例或三例ES是临床实践中对GDD/ID患者进行初步调查的更具成本效益的选择。根据这些最新的证据,我们提出了一种以ES作为无法解释的GDD/ID的第一层评估的评估算法。
