title: Next-generation sequencing-based molecular diagnosis of neonatal hypotonia in Chinese Population.
abstract: Neonatal hypotonia is extremely challenging to diagnose because numerous disorders present similar clinical manifestations. Two panels for diagnosing neonatal hypotonia were developed, which enriches 35 genes corresponding to 61 neonatal hypotonia-related disorders. A cohort of 214 neonates with hypotonia was recruited from 2012 to 2014 in China for this study. Of these subjects, twenty-eight neonates with hypotonia were eliminated according to exclusion criteria and 97 were confirmed using traditional detection methods. The clinical diagnoses of the remaining 89 neonates with hypotonia were approached by targeted next-generation sequencing (NGS). Among the 89 tested neonates, 25 potentially pathogenic variants in nine genes (RYR1, MECP2, MUT, CDKL5, MPZ, PMM2, MTM1, LAMA2 and DMPK) were identified in 22 patients. Six of these pathogenic variants were novel. Of the 186 neonates with hypotonia, we identified the genetic causes for 117 neonates by the traditional detection methods and targeted NGS, achieving a high solving rate of 62.9%. In addition, we found seven neonates with RETT syndrome carrying five mutations, thus expanding the mutation profiles in Chinese neonates with hypotonia. Our study highlights the utility of comprehensive molecular genetic testing, which provides the advantage of speed and diagnostic specificity without invasive procedures.
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Guo
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Shi
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Wan-Qiao
authors.initials: WQ
authors.lastname: Zhang
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Liu
authors.affiliation: Beijing CapitalBio Medical Laboratory, Beijing, 101111, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Deng
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Sun
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.|Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing, 100084, P.R. China.
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Xing
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, P.R. China.|CapitalBio Corporation, Beijing, 102206, P.R. China.|Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing, 100084, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: BaYi Children's Hospital, Beijing Military General Hospital, Beijing, 100700, P.R. China.
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Feng
mesh_terms: D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009123:Muscle Hypotonia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009468:Neuromuscular Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D057089:Pathology, Molecular / Q000379:methods; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology