Screening Of TTF2 (FOXE1) Gene Mutation In Children With Congenital Hypothyroidism And Hypothyroidism

Objective: To identify the types and characterstics of TTF2(FOXE1)mutations of congenital hypothyroidism(CH) in children with thyroid hypoplasia from Shandong area and to provide a theoretical basis for gene diagnosis and early treatment of CHMethods: We enrolled 90 patients of CH with dysgenesis in Shandong Province.Blood samples were collected from these 90 patients and they come from 90 unrelated families including 29 boys and 61 girls. Serum thyroid hormone testing revealed that TSH levels(≥20 μIU/m L) accompanied by low serum FT4 and FT3. Moreover, thyroid ultrasound examination revealed agenesis ectopy and hypoplastic. And then we extracted Genomic DNA. The exon sequences of TTF2 gene were amplified by PCR and the products were directly sequenced to find new mutations types of TTF2 gene.Results:A novel heterozygous missense variant, c.A3401G(p.K1134R), and a single nucleotide polymorphism(rs755282859, c.483G>A) in FOXE1 were identified in two CH patients with dysgenesis, which was not found in those 90 healthy control subjects. These two CH patients’ clinical pheontype were permanent and mild transient CH with dysgenesis, respectively.Conclusions: We identified a novel heterozygous missense FOXE1 variant in CH patients with dysgenesis.This is the first time to report the variant, and we susppect the variant was deleterious highly,which shows that the mutation rate of FOXE1 is very low.