Clinical Utility of Next-Generation Sequencing for Developmental Disorders in the Rehabilitation Department: Experiences
- PDF / 2,102,063 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 22 Downloads / 171 Views
Clinical Utility of Next-Generation Sequencing for Developmental Disorders in the Rehabilitation Department: Experiences from a Single Chinese Center Yun Liu 1 & Xiaomei Liu 1 & Dongdong Qin 2 & Yiming Zhao 3 & Xuanlan Cao 1 & Xiaoli Deng 1 & Yu Cheng 1 & Fuping Liu 1 & Fang Yang 4 & Tiesong Zhang 1 & Xiu-An Yang 3 Received: 26 July 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract This study investigated the clinical and genetic characteristics of developmental disorders (DDs) in children attending a rehabilitation department. A total of 94 children with suspected rare and undiagnosed DDs were included in this study. All patients were subjected to next-generation sequencing by means of proband single whole-exome sequencing (Pro-WES) or trio wholeexome sequencing (Trio-WES). To investigate the copy number variations (CNVs), 63 patients were subjected to the trio strategy, and 17 cases were subjected to the proband single strategy. The patients developed early and suffered from severe symptoms. WES reached a high diagnostic rate (48.7%, 46/94), and de novo (48.3%, 28/58) was the main pathogenic form. Most identified single-nucleotide variations (SNVs)/small insertions and deletions (indels) were found only in one patient. The number of uncertain significant locus in the patients taking Trio-WES was significantly lower than that in patients taking Pro-WES (2.1% vs 2.8%). Compared with hereditary mutations passed from parents, pathogenicity was more obvious in de novo mutations. The diagnostic rate of WES accompanied by CNVseq (57.5%, 46/80) was significantly higher (p = 0.016) than WES alone. Nextgeneration sequencing exhibited a satisfactory diagnostic rate for DDs patients in the rehabilitation department. Compared with the proband-only model, the family trio strategy should be employed more frequently because it can reduce the number of uncertain significant sites and help to identify de novo pathogenic mutations. Keywords Next-generation sequencing . Whole-genome sequencing . Copy number variation sequencing . Developmental disorders . Rehabilitation department
Introduction Developmental disorders (DDs) are a group of heterogeneous diseases, which are characterized by delays in global development, motor skills, cognition, and speech/language, as well as social/personal activities of daily living, affecting more than
3% of children (Bellman et al. 2013; Wright et al. 2015). When two or more of these developmental domains are involved, the patient will be diagnosed as global developmental delay (GDD) (Wright et al. 2015). GDD is an early-onset disease that affects children under 5 years of age and has a prevalence rate of 1% (Majnemer and Shevell 1995). Any
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01707-4) contains supplementary material, which is available to authorized users. * Tiesong Zhang [email protected]
2
Yunnan University of Chinese Medicine, Kunming 650500, Peo
Data Loading...
