Newborn Genetic Screening Improves the Screening Efficiency for Congenital Hypothyroidism: A Prospective Multicenter Study in China

Liang Ye; Yinhong Zhang; Jizhen Feng; Cidan Huang; Xiaohua Wang; Lianshu Han; Yonglan Huang; Hui Zou; Baosheng Zhu; Jingkun Miao

doi:10.3390/ijns10040078

Newborn Genetic Screening Improves the Screening Efficiency for Congenital Hypothyroidism: A Prospective Multicenter Study in China

Int J Neonatal Screen. 2024 Nov 29;10(4):78. doi: 10.3390/ijns10040078.

Authors

Liang Ye¹, Yinhong Zhang², Jizhen Feng³, Cidan Huang⁴, Xiaohua Wang⁵, Lianshu Han⁶, Yonglan Huang⁷, Hui Zou⁸, Baosheng Zhu², Jingkun Miao¹

Affiliations

¹ Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing 401147, China.
² Department of Medical Genetics, NHC Key Laboratory of Preconception Health in Western China, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650100, China.
³ Department of Genetic, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang 050006, China.
⁴ Neonatal Disease Screening Center, Hainan Women and Children's Medical Center, Haikou 570206, China.
⁵ Department of Genetics, Inner Mongolia Maternity and Child Health Care Hospital, Hohhot 750306, China.
⁶ Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
⁷ Department of Guangzhou Newborn Screening Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China.
⁸ Neonatal Disease Screening Center, Jinan Maternity and Child Health Hospital Affiliated to Shandong First Medical University, Jinan 250001, China.

PMID: 39728398
DOI: 10.3390/ijns10040078

Abstract

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns were prospectively recruited from eight hospitals in China between February and December 2021. Clinical characteristics were collected. Second-generation sequencing was used to detect four CH-related genes, and the genetic patterns of the pathogenic genes were analyzed. We analyzed the relationship between genotype and biochemical phenotype. A total of 29,601 newborns were screened for CH. Gene panel sequencing identified 18 patients, including 10 patients affected by biochemically and genetically screened disorders and 8 patients affected by solely genetically screened disorders. The predictive positive value of genetic screening was 34.62%, which was much greater than that of biochemical screening alone (17.99%). A total of 94 cases of congenital thyroid dysfunction were confirmed by biochemical and genetic screening, including 30 CHs and 64 isolated hyperthyrotropinemia (HTT), with an incidence of 1/987 for CH and 1/463 for HTT, and a total incidence of 1/315 for hypothyroidism. The incidence rate and number of patients in Jinan were the highest, and the incidence rates in Shijiazhuang and Shanghai were the lowest. The gene mutation rate in this study was 19.1%, mainly DUOX2 mutation. The most common variant of DUOX2 was c.1588A>T(p.Lys530*). There was only a difference in sFT4 between groups with gene mutations and those without mutations. Genetic screening is a supplement to biochemical screening. Combining biochemical screening with genetic screening is useful for improving screening efficiency. The incidence of CH in China according to a multicenter study of nearly 30,000 NBS surveys was 1/315. DUOX2 gene mutations are commonly detected in these patients.

Keywords: DUOX2; congenital hypothyroidism; genetic screening; newborn screening.

Abstract

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