DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population
2016; 36(2): 145-153
Ann Lab Med 2016; 36(6): 561-572
Published online November 1, 2016 https://doi.org/10.3343/alm.2016.36.6.561
Copyright © Korean Society for Laboratory Medicine.
Kyoung-Jin Park, M.D.1,*, Seungman Park, M.D.2, Eunhee Lee, M.D.2, Jong-Ho Park, B.S.1, June-Hee Park, B.S.3, Hyung-Doo Park, M.D.4, Soo-Youn Lee, M.D.4, and Jong-Won Kim, M.D.1,4
Department of Health Sciences and Technology1, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul; Green Cross Laboratories2, Yongin; Samsung Biomedical Research Institute3, Samsung Medical Center, Seoul; Department of Laboratory Medicine & Genetics4, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to: Jong-Won Kim
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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.
Keywords: Epidemiology, Founder mutation, Incidence, Inherited metabolic disease, Newborn screening, Next-generation sequencing