Hui Zou1, Jian Chai2, Shiguo Liu3, Hongwei Zang2, Xiaoxia Yu2, Liping Tian1, Huichao Li4, Bingjuan Han5. 1. 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. 2. Department of Biochemistry and Molecular Biology, Qingdao University Qingdao 266021, Shandong, China. 3. Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China. 4. Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China. 5. Neonatal Disease Screening Center, Jinan Maternity and Child Health Care Hospital Jinan 250001, Shandong, China.
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. AIM: To screen PAX8 mutations and characterize the features of these mutations in Chinese TD patients. MATERIALS AND 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. CONCLUSION: 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.
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. AIM: To screen PAX8 mutations and characterize the features of these mutations in Chinese TDpatients. MATERIALS AND METHODS: Blood samples were collected from 63 TDpatients 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. CONCLUSION: We report a heterozygous missense de novo mutation in PAX8 in one out of 63 unrelated Chinese TDpatients, showing that the PAX8 mutation rate is very low in TDpatients in China. However, de novo mutation and epigenetic mechanisms need to be considered in the future study.
Entities:
Keywords:
Congenital hypothyroidism; PAX8; de novo mutation; thyroid dysgenesis
Authors: Tina Di Palma; Roberto Nitsch; Anna Mascia; Lucio Nitsch; Roberto Di Lauro; Mariastella Zannini Journal: J Biol Chem Date: 2002-11-18 Impact factor: 5.157
Authors: Rebecca Perry; Claudine Heinrichs; Pierre Bourdoux; Khalil Khoury; François Szöts; Jean H Dussault; Gilbert Vassart; Guy Van Vliet Journal: J Clin Endocrinol Metab Date: 2002-09 Impact factor: 5.958
Authors: Pia Hermanns; Helmut Grasberger; Ronald Cohen; Clemens Freiberg; Helmuth-Günther Dörr; Samuel Refetoff; Joachim Pohlenz Journal: Thyroid Date: 2013-01-11 Impact factor: 6.568
Authors: P E Macchia; P Lapi; H Krude; M T Pirro; C Missero; L Chiovato; A Souabni; M Baserga; V Tassi; A Pinchera; G Fenzi; A Grüters; M Busslinger; R Di Lauro Journal: Nat Genet Date: 1998-05 Impact factor: 38.330