Sihombing Nydia Rena Benita, Winarni Tri Indah, de Leeuw Nicole, van Bon Bregje, van Bokhoven Hans, Faradz Sultana Mh
Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
Intractable Rare Dis Res. 2023 May;12(2):104-113. doi: 10.5582/irdr.2023.01001.
Intellectual disability (ID) and multiple congenital anomalies (MCA) are major contributors to infant mortality, childhood morbidity, and long-term disability, with multifactorial aetiology including genetics. We aim to set a diagnostic approach for genetic evaluation of patients with ID and MCA, which can be applied efficiently with a good diagnostic rate in Indonesia or other low resources settings. Out of 131 ID cases, twenty-three individuals with ID/global developmental delay (GDD) and MCA were selected from two-steps of dysmorphology screening and evaluation. Genetic analysis included chromosomal microarray (CMA) analysis, targeted panel gene sequencing, and exome sequencing (ES). CMA revealed conclusive results for seven individuals. Meanwhile, two out of four cases were diagnosed by targeted gene sequencing. Five out of seven individuals were diagnosed using ES testing. Based on the experience, a novel and comprehensive flowchart combining thorough physical and dysmorphology evaluation, followed by suitable genetic tests is proposed as a diagnostic approach to elucidate the genetic factor(s) of ID/GDD and MCA in low resources settings such as Indonesia.
智力残疾（ID）和多重先天性异常（MCA）是导致婴儿死亡、儿童发病和长期残疾的主要因素，其病因多为包括遗传学在内的多因素。我们旨在制定一种针对ID和MCA患者的基因评估诊断方法，该方法在印度尼西亚或其他资源匮乏地区能够高效应用且诊断率良好。在131例ID病例中，通过两步法的畸形筛查和评估，从23例患有ID/全面发育迟缓（GDD）和MCA的个体中进行了选择。基因分析包括染色体微阵列（CMA）分析、靶向基因panel测序和外显子组测序（ES）。CMA对7例个体得出了确定性结果。同时，4例中的2例通过靶向基因测序得以诊断。7例个体中有5例通过ES检测被诊断。基于这些经验，提出了一种新颖且全面的流程图，该流程图结合了全面的体格和畸形评估，随后进行适当的基因检测，作为在印度尼西亚等资源匮乏地区阐明ID/GDD和MCA遗传因素的诊断方法。
