Study on dual oxidase maturation factor 1 gene mutations in patients with congenital hypothyroidism combined with thyroid goiter / 中华实用儿科临床杂志

ABSTRACT

Objective To screen the dual oxidase maturation factor 1 (DUOXA1) gene mutations in children with congenital hypothyroidism (CH) and thyroid goiter from Shandong Province,China,and to identify the gene mutation type and characteristics of DUOXA1 gene mutations in order to provide some evidence for gene diagnosis and therapy of CH.Methods A cohort of 52 cases of CH with thyroid goiter and 100 normal controls were selected according to neonatal screening system in Shandong Province whose genomic DNA was isolated from peripheral blood leukocytes with a standard phenol chloroform method.The whole coding sequence (CDS) of DUOXA1 gene was amplified with 8 pairs of sequence specific primers by using PCR.The PCR products were directly sequenced with Sanger sequencing to detect new mutations types of DUOXA1 gene.The sequencing data were compared to the DUOXA1 gene reference sequence(National Center for Biotechnology InformationRefSeqNG_033105.1) to see if there was any mutation.Ax2 test was done for the gene frequency of discovered single nucleotide polymorphisms (SNP).Results There was no mutation in CDS of 52 CH patients with thyroid goiter and 100 normal controls.However,a SNP (rs75981505,c.398G ＞ T) which was an missense mutation and could lead to a change of the codon from CGC to CTC,was found in 9 CH patients with thyroid goiter and 11 normal controls in the exon 7.The corresponding amino acid arginine was replaced by histidine(p.Arg133His).There was no significant difference in the SNP rate between CH patients with thyroid goiter and normal controls (17.3％ vs 11.0％,x2 =1.24,P ＞ 0.05).Conclusion DUOXA1 gene mutation rate is very low which may not be the main cause of CH patients with thyroid goiter in the population of Shandong Province.