title: Genotypes and phenotypes of congenital goitre and hypothyroidism caused by mutations in dual oxidase 2 genes.
abstract: OBJECTIVE
  The aim of this study was to screen for DUOX2, TPO and TG mutations in Chinese patients with congenital hypothyroidism (CH) and goitre and to define the relationships between DUOX2 genotypes and clinical phenotypes.
  
  
  METHODS
  Blood samples were collected from 67 patients with CH and goitre in Shandong Province, China. Genomic DNA was extracted from peripheral blood leucocytes. PCR and direct sequencing were used to analyse all exons of DUOX2, TPO and TG. Detailed medical records were then collected, and the relationship between DUOX2 genotype and the clinical phenotype of CH and goitre caused by DUOX2 mutations was investigated.
  
  
  RESULTS
  Analysis of DUOX2 revealed nine mutations, including one novel nonsense mutation (p.W734X), six novel missense mutations (p.N100D, p.S660L, p.A1131S, p.W1181G, p.A1206T and p.R1267W) and two recurrent mutations (p.R701X and p.R1110Q) in 10 patients from 10 unrelated families. Monoallelic and compound heterozygous mutations in DUOX2 were associated with permanent or transient CH. No mutation was found after screening all exons of TPO and TG.
  
  
  CONCLUSIONS
  Our study identified DUOX2 mutations in 14·9% of Chinese patients investigated with CH and goitre. Because the relationships between DUOX2 genotypes and clinical phenotypes are extremely complex, however, further studies are needed to identify more mutations in known genes which are involved in CH and goitre.
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Kunna
authors.initials: K
authors.lastname: Lu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yang
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhang
authors.forename: Shiguo
authors.initials: S
authors.lastname: Liu
authors.forename: Shengli
authors.initials: S
authors.lastname: Yan
mesh_terms: D001324:Autoantigens / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000209:etiology / Q000235:genetics*; D000074623:Dual Oxidases; D005260:Female; D005838:Genotype; D006042:Goiter / Q000235:genetics*; D006801:Humans; D007223:Infant; D007453:Iodide Peroxidase / Q000235:genetics; D033862:Iron-Binding Proteins / Q000235:genetics; D008297:Male; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D010641:Phenotype; D013954:Thyroglobulin / Q000235:genetics
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; D013954:Thyroglobulin; D000074623:Dual Oxidases; C056658:TPO protein, human; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431515:DUOX2 protein, human