Abstract：Objective To study the features of DUOX2 mutations and genotype-phenotype relationship in children with congenital hypothyroidism (CH), in order to provide evidence for gene diagnosis and gene treatment of CH. Methods Blood samples were collected from 10 CH children with thyromegaly. Genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and direct sequencing. Results G3632A mutation in the exon 28 of DUOX2 that may result in arginine to histidine substitution at codon 1211 was found in one patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to arginine substitution at codon 678 was found in three patients. They were all heterozygous mutations. Conclusions Heterozygous mutations in DUOX2 may affect protein function and cause CH. The relationship between DUOX2 genotypes and clinical phenotypes is unclear and needs further studies.
De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms[J]. Endocr Rev, 2004, 25(5): 722-746.
[2]
Vilain C, Rydlewski C, Duprez L, et al. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-offunction mutation of PAX8[J]. J Clin Endocrinol Metab, 2001, 86(1): 234-238.
[3]
Van Vliet G. Development of the thyroid gland: lessons from congenitally hypothyroid mice and men[J]. Clin Genet, 2003, 63(6): 445-455.
[4]
Rubio IG, Galrao AL, Pardo V, et al. A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation[J]. Arq Bras Endocrinol Metabol, 2008, 52(8): 1337-1344.
[5]
Morand S, Agnandji D, Noel-Hudson MS, et al. Targeting of the dual oxidase 2 N-terminal region to the plasma membrane[J]. J Biol Chem, 2004, 279(29): 30244-30251.
[6]
Moreno JC, Pauws E, van Kampen AH, et al. Cloning of tissuespecific genes using serial analysis of gene expression and a novel computational substraction approach[J]. Genomics, 2001, 75(1-3): 70-76.
[7]
De Deken X, Wang D, Many MC, et al. Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family[J]. J Biol Chem, 2000, 275(30): 23227-233.
[8]
Dupuy C, Kaniewski J, Deme D, et al. NADPH-dependent H2O2 generation catalyzed by thyroid plasma membranes. Studies with electron scavengers[J]. Eur J Biochem, 1989, 185(3): 597-603.
[9]
Dupuy C, Virion A, De Sandro V, et al. Activation of the NADPH-dependent H2O2-generating system in pig thyroid particulate fraction by limited proteolysis and Zn2+ treatment[J]. Biochem J, 1992, 283(Pt 2): 591-595.
[10]
Vigone MC, Fugazzola L, Zamproni I, et al. Persistent mild hypothyroidism associated with novel sequence variants of the DUOX2 gene in two siblings[J]. Hum Mutat, 2005, 26(4): 395.
[11]
Vaisman M, Rosenthal D, Carvalho DP. Enzymes involved in thyroid iodide organification[J]. Arq Bras Endocrinol Metabol, 2004, 48(1): 9-15.
[12]
Moreno JC, Bikker H, Kempers MJ, et al. Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism[J]. N Engl J Med, 2002, 347(2): 95-102.
[13]
Varela V, Rivolta CM, Esperante SA, et al. Three mutations (p.Q36H, p.G418fsX482, and g.IVS19-2A>C) in the dual oxidase 2 gene responsible for congenital goiter and iodide organification defect[J]. Clin Chem, 2006, 52(2): 182-191.
[14]
Pfarr N, Korsch E, Kaspers S, et al. Congenital hypothyroidism caused by new mutations in the thyroid oxidase 2 (THOX2) gene[J]. Clin Endocrinol, 2006, 65(6): 810-815.
[15]
Chiesa A, Rivolta CM, Targovnik HM, et al. Clinical, biochemical, and molecular findings in Argentinean patients with goitrous congenital hypothyroidism[J]. Endocrine, 2010, 38(3): 377-385.
[16]
Maruo Y, Takahashi H, Soeda I, et al. Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2 gene in Japanese patients detected by a neonatal screening program[J]. J Clin Endocrinol Metab, 2008, 93(11): 4261-4267.
