title: A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening.
abstract: BACKGROUND
  A newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population.
  
  
  METHODS
  In total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects.
  
  
  RESULTS
  The overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT.
  
  
  CONCLUSIONS
  Through a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population.
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors: Kyoung Jin
authors: KJ
authors: Park
authors: Green Cross Laboratories, Yongin, Korea.
authors: Seungman
authors: S
authors: Park
authors: Green Cross Laboratories, Yongin, Korea.
authors: Eunhee
authors: E
authors: Lee
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors: Jong Ho
authors: JH
authors: Park
authors: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors: June Hee
authors: JH
authors: Park
authors: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Hyung Doo
authors: HD
authors: Park
authors: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Soo Youn
authors: SY
authors: Lee
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.|Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kimjw@skku.edu.
authors: Jong Won
authors: JW
authors: Kim
mesh_terms: D019295:Computational Biology; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D059788:Dried Blood Spot Testing; D005686:Galactokinase; D023281:Genomics; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics; D008659:Metabolic Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D015997:Neonatal Screening; D011110:Polymorphism, Genetic; D056910:Republic of Korea / Q000453:epidemiology; D017422:Sequence Analysis, DNA
chemical_list: C513411:DUOXA2 protein, human; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; C119629:SLC25A13 protein, human; D004247:DNA; D005686:Galactokinase
keywords: Epidemiology; Founder mutation; Incidence; Inherited metabolic disease; Newborn screening; Next-generation sequencing