Genetic characteristics of 58 children with unexplained developmental delay/intellectual disability analyzed by Trios-WES

FENG Jincai; ZHAO Tingting; JIA Jia; TIAN Yuan; SHAO Da; YU Guangjun

doi:10.11852/zgetbjzz2022-1361

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Chinese Journal of Child Health Care ›› 2023, Vol. 31 ›› Issue (8) : 889-894. DOI: 10.11852/zgetbjzz2022-1361

Genetic characteristics of 58 children with unexplained developmental delay/intellectual disability analyzed by Trios-WES

FENG Jincai¹, ZHAO Tingting², JIA Jia², TIAN Yuan³, SHAO Da⁴, YU Guangjun⁵

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Abstract

Objective To improve diagnostic accuracy of developmental delay/intellectual disability (DD/ID) using genetic variation analysis of single nucleotide variant (SNV)/small insertion-deletion (InDel) and copy number variant (CNV) based on Trios-whole-exome sequencing (Trios-WES). Methods From March 1st, 2017 to March 31st, 2019, 58 children with DD/ID were enrolled and analyzed by Trios-WES technique, who were treated in the High-Risk Infants Multi-Disciplinary Treatment Outpatient and Rehabilitation Department Outpatient of Shanghai Children's Hospital, and were assessed by Gesell, WPPIS-Ⅳ or WISC-Ⅳ as non-external factors, negative by conventional genetic tests, and with unexplained reasons. Further phenotypic confirmation and Sanger sequencing verification were performed to analyze the results. Results Among 58 unknown-cause children with DD/ID, 41 DD/ID related gene variants were identified by Trios-WES analysis and 13 genes variants were reported for the first time. Thirty-threegenes variants (33/58, 56.9%) were found to be pathogenic single genes or multiple gene variants, including three CNV variants and one paternal uniparental disomy (UPD). There were 10 missense variants, 7 splicing variants, 7 frameshift variants and 5 nonsense variants. The de novo variants accounted for 79% of all pathogenic variants. Among them, MECP2, TCF4, SYNGAP1, UBE3A and SHANK3 gene variants appeared frequently. Conclusions The clinical genetic testing strategy of Trios-WES analysis can improve the diagnosis rate of children with unexplained DD/ID, help to identify the cause, and provide a basis for further treatment and genetic counseling.

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developmental delay/intellectual disability / Trios-Whole-Exome Sequencing / genetic testing / genetic variation

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FENG Jincai, ZHAO Tingting, JIA Jia, TIAN Yuan, SHAO Da, YU Guangjun. Genetic characteristics of 58 children with unexplained developmental delay/intellectual disability analyzed by Trios-WES[J]. Chinese Journal of Child Health Care. 2023, 31(8): 889-894 https://doi.org/10.11852/zgetbjzz2022-1361

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