Ma Heqian, Zhu Lina, Yang Xiao, Ao Meng, Zhang Shunxiang, Guo Meizhen, Dai Xuelin, Ma Xiuwei, Zhang Xiaoying
The School of Public Health, Guilin Medical University, 1 Zhiyuan Road, Lingui District, 541199, Guilin, PR China.
Faculty of Pediatrics, The Chinese PLA General Hospital, 100700, Beijing, China.
BMC Genomics. 2024 Apr 22;25(1):391. doi: 10.1186/s12864-024-10279-1.
Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15-49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02-3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.
发育迟缓（DD）或智力残疾（ID）是一大类早发性疾病，影响全球1%-2%的儿童，其具有多种应予以识别的遗传病因。基因研究能够阐明DD/ID潜在的发病机制。在本研究中，对225名中国DD/ID儿童进行了全外显子组测序（WES）（208例按先证者-父母三联体进行测序），这些儿童被分为七个表型亚组。对DD/ID患者的表型和基因组数据进行了进一步回顾性分析。基于WES数据，发现96/225（42.67%；95%置信区间[CI] 36.15-49.18%）的患者具有与DD/ID相关的致病性单核苷酸变异（SNV）和小插入/缺失（Indel）。七个亚组中的诊断率在31.25%至71.43%之间。听力丧失、视力丧失和面部畸形这三个特定临床特征可显著提高DD/ID患者WES的诊断率（分别为P = 0.005、P = 但005和P = 0.039）。值得注意的是，听力丧失（优势比[OR] = 1.86%；95% CI = 1.00-3.46，P = 0.046）或异常脑干听觉诱发电位（BAEP）（OR = 1.91，95% CI = 1.02-3.50，P = 0.042）与DD/ID儿童的致病性基因变异独立相关。我们的研究结果丰富了与DD/ID相关的SNV/Indel变异谱，突出了DD/ID儿童基因检测的价值，强调了BAEP筛查在DD/ID儿童中的重要性，并有助于促进早期诊断、临床管理和生殖决策，改善对医疗治疗的反应。
