Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (9): 43-49.doi: 10.6040/j.issn.1671-7554.0.2025.0958

• Clinical Medicine • Previous Articles    

Application of whole exome sequencing technology in the clinical diagnosis and treatment of genetic diseases in children

WU Mingli1, JIANG Mingdi1, LI Jing2, SONG Chao1, LIU Jing1, LI Zhen1, ZHOU Yilin1, ZHANG Hong3, LIU Qinghua1   

  1. 1. Department of Clinical Laboratory;
    2. Department of Pediatrics;
    3. Department of Hematology, The Second Affiliated Hospital of Shandong First Medical University, Taian 271016, Shandong, China
  • Published:2026-09-09

PDF (PC)

3

Abstract: Objective To explore the value of whole exome sequencing(WES)in the clinical diagnosis and treatment of children with genetic diseases. Methods The clinical data of 265 children with suspected genetic diseases who visited the The Second Affiliated Hospital of Shandong First Medical University from March 2019 to August 2023 were retrospectively analyzed. All patients underwent WES sequencing analysis. Candidate variants were screened based on the clinical phenotypes of the children, and Sanger sequencing was used for verification. Pathogenicity assessment and genetic diagnosis were completed according to the guidelines of the American College of Medical Genetics and Genomics(ACMG). The overall detection rate of WES was determined based on phenotype categories, inheritance patterns, mitochondrial genome variations, and copy number variations, and the impact of WES on clinical diagnosis and treatment strategies was analyzed. Results Among the 265 children, 98 positive cases were detected, with a total detection rate of 37.0%(98/265). A total of 102 pathogenic or likely pathogenic single nucleotide variations, 20 copy number variations, 1 mitochondrial variation, and 31 de novo mutation sites were detected. In the context of clinical phenotypes, neurological diseases accounted for the highest proportion, reaching 55.5%(147/265). Based on the sequencing results, 61 children(62.3%)received individualized precision medical treatment. Conclusion WES technology is of great significance in revealing the genetic characteristics of children, facilitating early diagnosis, and providing personalized precision treatment plans.

Key words: Whole exome sequencing technology, Children, Genetic diseases, Diagnosis, Treatment, Single nucleotide variations, Copy number variations

CLC Number: 

  • R725.9
[1] Smith L D, Willig L K, Kingsmore S F. Whole-exome sequencing and whole-genome sequencing in critically ill neonates suspected to have single-gene disorders[J]. Cold Spring Harb Perspect Med, 2015, 6(2): a023168. DOI:10.1101/cshperspect.a023168
[2] 左伋, 张学. 医学遗传学[M]. 8版. 北京: 人民卫生出版社, 2024: 8.
[3] 荆梦霞, 余永国. 分子检测技术在儿童罕见遗传病中的临床应用[J]. 检验医学, 2024, 39(2): 103-106. Jing Mengxia, Yu Yongguo. Clinical application of different molecular detection techniques in childrens rare genetic diseases[J]. Laboratory Medicine, 2024, 39(2): 103-106.
[4] Georget M, Pisan E. Next generation sequencing(NGS)for beginners[J]. Rev Mal Respir, 2023, 40(4): 345-358.
[5] 中华儿科杂志编辑委员会. 儿童遗传病遗传检测临床应用专家共识[J]. 中华儿科杂志, 2019, 57(3): 172-176. The Editorial Board, Chinese Journal of Pediatrics. Consensus recommendations for the clinical application of genetic testing for childrens genetic[J]. Chinese Journal of Pediatrics, 2019, 57(3): 172-176.
[6] Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424.
[7] Gilissen C, Hehir-Kwa J Y, Thung D T, et al. Genome sequencing identifies major causes of severe intellectual disability[J]. Nature, 2014, 511(7509): 344-347.
[8] Wojcik M H, Lemire G, Berger E, et al. Genome sequencing for diagnosing rare diseases[J]. N Engl J Med, 2024, 390(21): 1985-1997.
[9] Skoczylas S, Poszaj T, Gadzalska K, et al. Mitochon-drial DNA variants revealed by whole exome sequencing: from screening to diagnosis and follow-up[J]. Neurogenetics, 2025, 26(1): 38. DOI:10.1007/s10048-025-00820-z
[10] Sun G G, Huang W, Wang L, et al. Molecular findings in patients for whole exome sequencing and mitochondrial genome assessment[J]. Clin Chim Acta, 2024, 561: 119774. DOI:10.1016/j.cca.2024.119774
[11] Srivastava S, Love-Nichols J A, Dies K A, et al. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders[J]. Genet Med, 2019, 21(11): 2413-2421.
[12] Lan X P, Tang X J, Weng W H, et al. Diagnostic utility of trio-exome sequencing for children with neurodevelopmental disorders[J]. JAMA Netw Open, 2025, 8(3): e251807. DOI:10.1001/jamanetworkopen.2025.1807
[13] 张丽, 高姚怡, 郁俐, 等. 全外显子组测序技术在成人遗传病中的应用[J]. 中华检验医学杂志, 2024, 47(10): 1192-1196. Zhang Li, Gao Yaoyi, Yu Li, et al. Analysis of whole exome sequencing result in adult genetic diseases[J]. Chinese Journal of Laboratory Medicine, 2024, 47(10): 1192-1196.
[14] Cao L, Huang X J, Wang N, et al. Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China[J]. Transl Neurodegener, 2021, 10(1): 7. DOI:10.1186/s40035-021-00231-8
[15] Hannibal L, Jacobsen D W. Intracellular processing of vitamin B12 by MMACHC(CblC)[M] //Vitamin B12. Amsterdam: Elsevier, 2022: 275-298. DOI:10.1016/bs.vh.2022.02.001
[16] Aukema S M, Vandenput K, Scarano E, et al. Growth hormone treatment in patients with KBG syndrome: novel insights, challenges and recommendations from six new patients and literature review[J]. Am J Med Genet A, 2025, 197(12): e64168. DOI:10.1002/ajmg.a.64168
[17] Smith A C, Neveling K, Kanagal-Shamanna R. Optical genome mapping for structural variation analysis in hematologic malignancies[J]. Am J Hematol, 2022, 97(7): 975-982.
[18] 陈奕, 杨莹, 牛雪阳, 等. CASK基因变异相关的癫痫性脑病4例临床表型特点研究[J]. 中国实用儿科杂志, 2021, 36(4): 275-280. Chen Yi, Yang Ying, Niu Xueyang, et al. Clinical features of epileptic encephalopathy caused by CASK gene variants[J]. Chinese Journal of Practical Pediatrics, 2021, 36(4): 275-280.
[19] McKnight D, Morales A, Hatchell K E, et al. Genetic testing to inform epilepsy treatment management from an international study of clinical practice[J]. JAMA Neurol, 2022, 79(12): 1267-1276.
[20] de Grado A, Pisciotta C, Saveri P, et al. Will new investigational drugs change the way we treat Charcot-Marie-Tooth disease?[J]. Expert OpinInvestig Drugs, 2024, 33(7): 653-656.
[21] Inozyme Pharma, Inc. Inozymes INZ-701 receives FDA fast track designation for ABCC6 deficiency[EB/OL].[2024-07-02] (2025-08-13). https://www.rttnews.com/3457736/inozyme-s-inz-701-receives-fda-fast-track-designation-for-abcc6-deficiency.aspx
[22] 李妍, 郝晔. 治疗Rett综合征的首个新药: Daybue[J]. 中国临床药理学杂志, 2024, 40(18): 2743-2746. Li Yan, Hao Ye. Daybue, the first new drug for the treatment of Rett syndrome[J]. The Chinese Journal of Clinical Pharmacology, 2024, 40(18): 2743-2746.
[23] Schambach A, Buchholz C J, Torres-Ruiz R, et al. A new age of precision gene therapy[J]. Lancet, 2024, 403(10426): 568-582.
[24] Azidane S, Gallego X, Durham L, et al. Identification of novel driver risk genes in CNV loci associated with neurodevelopmental disorders[J]. HGG Adv, 2024, 5(3): 100316. DOI:10.1016/j.xhgg.2024.100316
[25] Atli E I, Yalcintepe S, Atli E, et al. Clinical implications of chromosome 16 copy number variation[J]. Mol Syndromol, 2022, 13(3): 184-192.
[26] Arslan A B, Zamani A G, Yıldırım M S. Novel findings, mini-review and dysmorphological characterization of 16p13.11 microduplication syndrome[J]. Int J Dev Neurosci, 2022, 82(4): 289-294.
[27] Allach El Khattabi L, Heide S, Caberg J H, et al. 16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations[J]. J Med Genet, 2020, 57(5): 301-307.
[28] Wojcik M H, Lemire G, Berger E, et al. Genome sequencing for diagnosing rare diseases[J]. N Engl J Med, 2024, 390(21): 1985-1997.
[29] Ewans L J, Schofield D, Shrestha R, et al. Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders[J]. Genet Med, 2018, 20(12): 1564-1574.
[30] Jalkh N, Corbani S, Haidar Z, et al. The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population[J]. BMC Med Genomics, 2019, 12(1): 11. DOI:10.1186/s12920-019-0474-y
[1] LV Yan-Feng, DING Ke, WANG Jian-Xin, YU Hua-Long, BEI Shao-Sheng. Canceration of chronic anal fistula [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 55-57.
[2] LI Bo-Bo, LI Dao-Tang, LIU Shu-Guang, WANG Xing-Wu. Expression of serum DKK-1 in esophageal cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 58-61.
[3] XU Ping, YU Guo-Fang, LI Xia. Differential diagnosis of Graves′ disease and Hashimoto′s thyroiditis by different types peak systolic velocity of the superior thyroid artery [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 62-64.
[4] WANG Xin, XING Chun-Yan, YANG Yan-Ping. Serum phosphopyruvate hydratase in diagnosis of invasive Candida albicans infection [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 92-94.
[5] FENG Jian, YANG Li, WANG Yongjun, LIU Changqing, TIAN Meina, ZHOU Han, YU Lianlong. Association between serum uric acid and metabolic syndrome in children and adolescents: a cross-sectional study in Shandong and Hebei provinces, China [J]. Journal of Shandong University (Health Sciences), 2026, 64(8): 96-106.
[6] XUE Ning, WEI Xuxia, XU Junjie, TANG Yunping, YANG Lu. Clinical characteristics and prognosis influencing factors of Clostridium difficile infection in children of different age groups [J]. Journal of Shandong University (Health Sciences), 2026, 64(7): 55-62.
[7] MA Yihan, YUAN Xinyun, LI Jiani, HAN Xu, DIAO Qidi, WANG Yan, CHU Xu, ZHANG Kun, HU Lei. Relationship between childhood abuse and frequent nightmares in adults with depressive disorders: mediating effect of somatic symptoms and moderating role of social support [J]. Journal of Shandong University (Health Sciences), 2026, 64(5): 96-105.
[8] YANG Jing, ZHANG Lei. Early childhood multi-niche viromes: unclassified phage diversity and host features [J]. Journal of Shandong University (Health Sciences), 2026, 64(5): 116-124.
[9] SUN Honglin, GUAN Yuqiang, YU Peiru, LI Lei, DU Qingxia, DING Hao. Feasibility and short-to-medium-term efficacy of stent implantation for the treatment of aortic coarctation complicated by hypertension in children [J]. Journal of Shandong University (Health Sciences), 2026, 64(4): 58-62.
[10] KUANG Li, XU Heyan. From precision assessment to integrated intervention: innovations and future perspectives in the diagnostic and therapeutic paradigm for child and adolescent mental health disorders [J]. Journal of Shandong University (Health Sciences), 2026, 64(3): 10-16.
[11] LI Fanghua, LIU Na, LI Xiaoyu, XU Dianhua, WANG Qian. Research progress on medication adherence in children and adolescents with depressive disorder [J]. Journal of Shandong University (Health Sciences), 2026, 64(3): 24-34.
[12] SUN Jiali, WANG Liang, WANG Changfeng, ZHANG Jie, GUO Lei. Emotional and behavioral problems in children with Klippel-Trenaunay syndrome: characteristics and influencing factors [J]. Journal of Shandong University (Health Sciences), 2026, 64(3): 78-82.
[13] WANG Qian, HU Xiaojing, WANG Aiqing, SUN Qiang, MENG Chunyan, LI Fanghua. Visual analysis of non-suicidal self-injury literature about children and adolescents with depressive disorder [J]. Journal of Shandong University (Health Sciences), 2026, 64(3): 93-107.
[14] Intelligent Orthopedics Subgroup of Chinese Association of Orthopedic, Subgroup for Prevention and Control of Spinal and Spinal Cord Injury Diseases of Professional Committee for Prevention and Control of Spinal Diseases of Chinese Preventive Medicine Association. Expert consensus on measurement sites and annotation of artificial intelligence-based spinal degenerative imaging(2025) [J]. Journal of Shandong University (Health Sciences), 2026, 64(2): 1-10.
[15] JI Xinyu, YU Siyi, SUN Yuanyuan, JI Bing. Orthopedic disease diagnosis and treatment assistance methods based on artificial intelligence and gait analysis [J]. Journal of Shandong University (Health Sciences), 2026, 64(2): 34-43.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd