Yang Eun Hye, Shin Yong Beom, Choi Soo Han, Yoo Hye Won, Kim Hye Young, Kwak Min Jung, Park Kyung Hee, Bae Mi Hye, Kong Ju Hyun, Lee Yun-Jin, Nam Sang Ook, Kim Young Mi
Department of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, South Korea.
Department of Rehabilitation, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, South Korea, Busan, South Korea.
Front Pediatr. 2021 Sep 15;9:690493. doi: 10.3389/fped.2021.690493. eCollection 2021.
Chromosomal microarray (CMA) is a first-tier genetic test for children with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA). In this study, we report our experiences with the use of CMA in Korean children with unexplained DD/ID. We performed CMA in a cohort of 308 children with DD/ID between January 2010 and September 2020. We also retrospectively reviewed their medical records. The Affymetrix CytoScan 750 K array with an average resolution of 100 kb was used to perform CMA. Comorbid neurodevelopmental disorders were ASD (37 patients; 12.0%), epilepsy (34 patients; 11.0%), and attention deficit hyperactivity disorders (12 patients; 3.9%). The diagnostic yield was 18.5%. Among the 221 copy number variants (CNVs) identified, 70 CNVs (57 patients; 18.5%) were pathogenic. Deletion CNVs were more common among pathogenic CNVs (PCNVs) than in non-PCNVs ( < 0.001). The size difference between PCNVs and non-PCNVs was not significant ( = 0.023). The number of included genes within CNV intervals was significantly higher in PCNVs (average 8.6; 0-347) than in non-PCNVs (average 47.5; 1-386) ( < 0.001). Short stature and hearing difficulty were also more common in the PCNV group than in the non-PCNV group ( = 0.010 and 0.070, respectively). This study provides additional evidence for the usefulness of CMA in genetic testing of children with DD/ID in Korea. The pathogenicity of CNVs correlated with the number of included genes within the CNV interval and deletion type of the CNVs, but not with CNV size.
染色体微阵列分析（CMA）是对发育迟缓（DD）、智力障碍（ID）、自闭症谱系障碍（ASD）和多发先天性异常（MCA）儿童进行的一级基因检测。在本研究中，我们报告了在韩国不明原因的DD/ID儿童中使用CMA的经验。2010年1月至2020年9月期间，我们对308名DD/ID儿童进行了CMA检测。我们还回顾性地查阅了他们的病历。使用平均分辨率为100 kb的Affymetrix CytoScan 750 K芯片进行CMA检测。共患的神经发育障碍包括ASD（37例；12.0%）、癫痫（34例；11.0%）和注意缺陷多动障碍（12例；3.9%）。诊断率为18.5%。在鉴定出的221个拷贝数变异（CNV）中，70个CNV（57例；18.5%）具有致病性。与非致病性CNV相比，缺失型CNV在致病性CNV（PCNV）中更常见（<0.001）。PCNV与非PCNV的大小差异不显著（=0.023）。CNV区间内包含的基因数量在PCNV中（平均8.6；0 - 347）显著高于非PCNV（平均47.5；1 - 386）（<0.001）。身材矮小和听力障碍在PCNV组中也比非PCNV组更常见（分别为=0.010和0.070）。本研究为CMA在韩国DD/ID儿童基因检测中的应用提供了更多证据。CNV的致病性与CNV区间内包含的基因数量以及CNV的缺失类型相关，但与CNV大小无关。
