title: High prevalence of DUOX2 gene mutations among children with congenital hypothyroidism in central China.
abstract: Congenial hypothyroidism (CH) is the most common congenital endocrine disease and is treatable when recognized early enough. We investigated the genetic variants in 12 children diagnosed with CH by newborn screening in Huangshi area central China. Twelve genes commonly involved in CH development were studied. Genomic DNA from peripheral blood was used to amplify all exons of the selected genes, and the constructed sequencing libraries were subjected to next generation high throughput DNA sequencing (NGS). Analysis of the sequencing results identified rare genetic variants in 11 of the 12 patients (91.7%), and two novel rare variants were found in DUOX2 gene and two in TPO gene. Mutations in DUOX2 gene were identified in 10 patients (83.3%), and all these patients were found to carry bi-allelic, tri-allelic mutations or compound mutations with other genes. Recurrent DUOX2 mutations include K530X, R683L, R1110Q, and L1343F. Truncating, splicing, and proven deleterious DUOX2 missense mutations were detected in 50% of the patients. Mutations in TG gene were identified in four patients, and mutations in TPO, THSR, SLC26A4 genes were identified, one in each patient, respectively. The high prevalence of DUOX2 mutations in this cohort of children with CH appears striking and surprising. The clinical implications were discussed.
authors: Department of Laboratory Medicine and Center of Newborn Screening, Huangshi Women and Children Hospital, Huangshi, Hubei, China.
authors: Hong
authors: H
authors: Jiang
authors: Department of Pediatrics, Lichuan Nationalities Women and Children Hospital, Lichuan, Hubei, China.
authors: Jinhua
authors: J
authors: Wu
authors: Department of Pediatrics, Huangshi Women and Children Hospital, Huangshi, Hubei, China.
authors: Shengzhong
authors: S
authors: Ke
authors: Labway Clinical Laboratories Inc., Shanghai, China.
authors: Yue
authors: Y
authors: Hu
authors: Department of Laboratory Medicine and Center of Newborn Screening, Huangshi Women and Children Hospital, Huangshi, Hubei, China.
authors: Anxing
authors: A
authors: Fei
authors: Labway Clinical Laboratories Inc., Shanghai, China.
authors: Yan
authors: Y
authors: Zhen
authors: Department of Radiology, Huangshi Women and Children Hospital, Huangshi, Hubei, China. Electronic address: hsyujin@126.com.
authors: Jin
authors: J
authors: Yu
authors: Labway Clinical Laboratories Inc., Shanghai, China. Electronic address: kzhu68@hotmail.com.
authors: Kuichun
authors: K
authors: Zhu
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D002681:China; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000503:physiopathology; D000074623:Dual Oxidases; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D015997:Neonatal Screening
chemical_list: D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human
keywords: Ampliseq; Congenital hypothyroidism; DUOX2; Dyshormonogenesis; NGS