title: A De novo PAX8 mutation in a Chinese child with congenital thyroid dysgenesis.
abstract: BACKGROUND
  Thyroid dysgenesis (TD) is the most frequent cause of congenital hypothyroidism (CH), but its pathogenesis remains unclear. As a thyroid transcription factor, paired box transcription factor 8 (PAX8) is essential for thyroid organogenesis and development.
  
  
  OBJECTIVE
  To screen PAX8 mutations and characterize the features of these mutations in Chinese TD patients.
  
  
  METHODS
  Blood samples were collected from 63 TD patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Exon 3~4 of PAX8 were analyzed by PCR and direct sequencing.
  
  
  RESULTS
  Direct sequencing of PAX8 revealed a heterozygous missense mutation (c.155G/C, P.Arg52Pro) in one child with agenesis. Genetic screening of the child's family revealed that the clinically unaffected parents do not carry the mutation, suggesting that the identified sequence change is a de novo mutation.
  
  
  CONCLUSIONS
  We report a heterozygous missense de novo mutation in PAX8 in one out of 63 unrelated Chinese TD patients, showing that the PAX8 mutation rate is very low in TD patients in China. However, de novo mutation and epigenetic mechanisms need to be considered in the future study.
authors.affiliation: Jinan Maternity and Child Health Care Hospital of Shandong University, Jinan 250100 Shandong, China ; Neonatal Disease Screening Center, Jinan Maternity and Child Health Care Hospital Jinan 250001, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Biochemistry and Molecular Biology, Qingdao University Qingdao 266021, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chai
authors.affiliation: Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China.
authors.forename: Shiguo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Qingdao University Qingdao 266021, Shandong, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zang
authors.affiliation: Department of Biochemistry and Molecular Biology, Qingdao University Qingdao 266021, Shandong, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yu
authors.affiliation: Jinan Maternity and Child Health Care Hospital of Shandong University, Jinan 250100 Shandong, China ; Neonatal Disease Screening Center, Jinan Maternity and Child Health Care Hospital Jinan 250001, Shandong, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Li
authors.affiliation: Neonatal Disease Screening Center, Jinan Maternity and Child Health Care Hospital Jinan 250001, Shandong, China.
authors.forename: Bingjuan
authors.initials: B
authors.lastname: Han
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D000072636:PAX8 Transcription Factor / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050033:Thyroid Dysgenesis / Q000235:genetics*
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human
keywords: Congenital hypothyroidism; PAX8; de novo mutation; thyroid dysgenesis