Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China

Background and methods: Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution singl...

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Main Authors: Rongyue Wang, Tingying Lei, Fang Fu, Ru Li, Xiangyi Jing, Xin Yang, Juan Liu, Dongzhi Li, Can Liao
Format: Article
Language:English
Published: Elsevier 2019-02-01
Series:Pediatrics and Neonatology
Online Access:http://www.sciencedirect.com/science/article/pii/S1875957217303170
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author Rongyue Wang
Tingying Lei
Fang Fu
Ru Li
Xiangyi Jing
Xin Yang
Juan Liu
Dongzhi Li
Can Liao
author_facet Rongyue Wang
Tingying Lei
Fang Fu
Ru Li
Xiangyi Jing
Xin Yang
Juan Liu
Dongzhi Li
Can Liao
author_sort Rongyue Wang
collection DOAJ
description Background and methods: Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. Results: A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Conclusion: Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Key Words: developmental delay, intellectual disability, chromosome microarray analysis, CNVs, microdeletion/microduplication
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spelling doaj-art-9f63bce11e594fe1bd6e5b6579cd1f1e2025-08-20T02:00:42ZengElsevierPediatrics and Neonatology1875-95722019-02-01601354210.1016/j.pedneo.2018.03.006Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South ChinaRongyue Wang0Tingying Lei1Fang Fu2Ru Li3Xiangyi Jing4Xin Yang5Juan Liu6Dongzhi Li7Can Liao8Southern Medical University, Guangzhou, 510515, Guangdong, China; The Second Hospital affiliated to Wenzhou Medical University, Wenzhou, 325035, Zhejiang, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaFoshan Women and Children's Hospital, Foshan, 528000, Guangdong, ChinaDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, ChinaSouthern Medical University, Guangzhou, 510515, Guangdong, China; Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China; Corresponding author. Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, No. 9 Jinsui Road, Guangzhou, China. Fax: +86 02038076078.Background and methods: Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. Results: A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Conclusion: Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Key Words: developmental delay, intellectual disability, chromosome microarray analysis, CNVs, microdeletion/microduplicationhttp://www.sciencedirect.com/science/article/pii/S1875957217303170
spellingShingle Rongyue Wang
Tingying Lei
Fang Fu
Ru Li
Xiangyi Jing
Xin Yang
Juan Liu
Dongzhi Li
Can Liao
Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
Pediatrics and Neonatology
title Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
title_full Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
title_fullStr Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
title_full_unstemmed Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
title_short Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China
title_sort application of chromosome microarray analysis in patients with unexplained developmental delay intellectual disability in south china
url http://www.sciencedirect.com/science/article/pii/S1875957217303170
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