Application of single nucleotide polymorphism-microarray and target gene sequencing in the study of genetic etiology of children with unexplained intellectual disability or developmental delay
10.3760/cma.j.issn.0578-1310.2016.10.006
- VernacularTitle:联合应用微阵列和目标基因捕获测序技术对不明原因智力障碍或发育迟缓患儿的诊断价值
- Author:
Zhijie GAO
1
;
Qian JIANG
;
Dazhi CHENG
;
Xiuxian YAN
;
Qian CHEN
;
Keming XU
Author Information
1. 首都儿科研究所附属儿童医院神经内科
- Keywords:
Developmental disabilities;
DNA copy number variations;
Mutation;
Next-generation sequencing
- From:
Chinese Journal of Pediatrics
2016;54(10):740-745
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the application of single nucleotide polymorphism (SNP)-microarray and target gene sequencing technology in the clinical molecular genetic diagnosis of unexplained intellectual disability(ID) or developmental delay (DD).Method Patients with ID or DD were recruited in the Department of Neurology,Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and February 2016.The intellectual assessment of the patients was performed using 0-6-year-old pediatric examination table of neuropsychological development or Wechsler intelligence scale (＞6 years).Patients with a DQ less than 49 or IQ less than 51 were included in this study.The patients were scanned by SNP-array for detection of genomic copy number variations (CNV),and the revealed genomic imbalance was confirmed by quantitative real time-PCR.Candidate gene mutation screening was carried out by target gene sequencing technology.Causal mutations or likely pathogenic variants were verified by polymerase chain reaction and direct sequencing.Result There were 15 children with ID or DD enrolled,9 males and 6 females.The age of these patients was 7 months-16 years and 9 months.SNP-array revealed that two of the 15 patients had genomic CNV.Both CNV were de novo micro deletions,one involved 11q24.1q25 and the other micro deletion located on 21q22.2q22.3.Both micro deletions were proved to have a clinical significance due to their association with ID,brain DD,unusual faces etc.by querying Decipher database.Thirteen patients with negative findings in SNP-array were consequently examined with target gene sequencing technology,genotype-phenotype correlation analysis and genetic analysis.Five patients were diagnosed with monogenic disorder,two were diagnosed with suspected genetic disorder and six were still negative.Conclusion Sequential use of SNP-array and target gene sequencing technology can significantly increase the molecular genetic etiologic diagnosis rate of the patients with unexplained ID or DD.Combined use of these technologies can serve as a useful examinational method in assisting differential diagnosis of children with unexplained ID or DD.
