Genetic analysis for 5 congenital hypothyroidism patients due to dyshormonogenesis

Objective To analyze molecular characteristics of 5 congenital hypothyroidism (CH) patients due to dyshormonogenesis. Method We enrolled 5 CH patients due to dyshormonogenesis who were identified in Newborn Screening Center of Guangxi Zhuang Autonomous Region, China. Blood samples were collected from the patients and their parents, and genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2, TG, TPO and NIS gene together with their exon-intron boundaries were screened by next-generation sequencing. Specimens from 100 normal controls were tested for these novel variations. Result No TPO, NIS or TG gene mutations were identified. Direct sequencing of the DUOX2 gene revealed that patient 1 had a compound heterozygote for c. 3340delC and p. R683L, patient 2 was homozygous for p. K530X and patient 3 was a heterozygote for p. E879K. Both biallelic and monoallelic heterozygous mutations in DUOX2 were associated with transient CH. Novel mutations included c. 3340delC and p. R683L, analysis of 100 healthy subjects without thyroid disease did not show the same change. Conclusion Genetic analysis of TPO, NIS, DUOX2 and TG gene in 5 unrelated CH patients with thyroid dyshormonogenesis revealed two novel DUOX2 mutations, both were biallelic and monoallelic heterozygous mutations in DUOX2 associated with transient CH. Key words: Hypothyroidism; Mutation; Dual oxidase 2 gene; Molecular genetics