{"id":310,"title":"Evaluation of Diagnostic Yield and Clinical Utility of Trio Whole-Genome Sequencing in Children With GDD/IDD in China","title_zh":"中国全面性发育迟缓/智力发育障碍儿童家系三联全基因组测序的诊断率与临床效用评估","url":"https://pubmed.ncbi.nlm.nih.gov/42974803","doi":"10.1111/cge.70255","pmid":"42974803","journal":"Clin Genet","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:04+00:00","authors":["Zhang J","Chen Z","Zhang Y","Liu Y","Guo Y","Zhang H","Zeng X","Lin X","Meng L","Zeng T","Yu W","Chen C","He X","Wang C","Zhai Q"],"primary_topic":"repro-genetics","topics":[{"slug":"pgt","score":1.0,"hits":["preimplantation genetic"]}],"topic_score":1.0,"preference_score":8.0,"preference_labels":["早期胚胎表观基因组 / 染色质"],"llm_score":63.0,"final_score":71.0,"score_dims":{"novelty":55,"rigor":76,"impact":52,"relevance":42,"translation":62},"recommend_reason":"对P GT前的遗传学病因诊断与再生育路径有直接参考价值（7例家庭转入PGT），诊断率与变异谱数据翔实；但本质为儿科神经遗传病队列，与ART/胚胎实验室核心环节距离较远，方法学亦无突破。","keywords":["三联全基因组测序","全面性发育迟缓","智力发育障碍","拷贝数变异","植入前遗传学检测","遗传咨询"],"selected":1,"story_id":133,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-endo-genetics","source_name":"PubMed · 生殖内分泌/遗传/保存","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该单中心队列研究纳入2018—2023年中国122例全面性发育迟缓/智力发育障碍（GDD/IDD）儿童，行家系三联全基因组测序（Trio-WGS）。总体诊断率为39.3%（48/122），检出35个SNV/Indel与13个CNV，其中新发变异占75%（36/48），以常染色体显性遗传为主。富集分析显示，除神经发育通用特征外，诊断基因集还特异富集于突触前功能、GABA能/氯离子转运与染色质重塑通路。多学科团队据此调整管理：3例经靶向治疗改善、30例调整合并症管理、17例修改饮食、7个家庭选择植入前遗传学检测。研究提示Trio-WGS可提高GDD/IDD遗传诊断率并为治疗与再生育指导提供依据，但缺乏对照与成本效果分析。","summary":"Accurate diagnosis and timely intervention are essential for improving outcomes in children with global developmental delay (GDD) or intellectual developmental disorder (IDD). Although genomic sequencing has improved diagnostic yield, studies integrating long-term clinical follow-up remain limited, hindering clinical translation. In this cohort study, 122 Chinese children with GDD/IDD were enrolled from a single center (2018-2023) and underwent Trio whole-genome sequencing (Trio-WGS). Trio-WGS achieved a 39.3% (48/122) diagnostic yield, identifying pathogenic/likely pathogenic variants in 48 cases, including 35 SNVs/Indels and 13 CNVs. De novo variants accounted for 75% (36/48) of findings, with autosomal dominant inheritance predominant. Enrichment analysis revealed that, beyond the generic neurodevelopmental signature, the GDD/IDD diagnostic gene set was specifically enriched for presynaptic function, GABAergic/chloride transport, and chromatin remodeling. A multidisciplinary team used results to optimize care: 3 children improved with targeted therapy, 30 had comorbidity management adjusted, 17 received diet modifications, and 7 families pursued preimplantation genetic testing. This study holds great significance for improving the genetic diagnosis rate of GDD/IDD and identifying new mutations, while also providing valuable information for the treatment of GDD/IDD and reproductive guidance.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}