A Study Of Gene Mutation In The Patients Of Congenital Hypothyroidism

Congenital hypothyroidism is the most common congenital endocrinediseases and can result in severe neurodevelopmental damnification andmental retardation if the patients are not diagnosed and treated in time. Theincidence of congenital hypothyroidism is at range of1:2,000to1:4,000for newborns. There are two classifications of the cause of congenitalhypothyroidism: thyroid dysgenesis and dyshormonogenesis. In recentyears, numbers of studies have found that mutations in genes which takepart in the development of thyroid follicular cells or thyroid hormonesynthesis pathway, can lead to changes of those encoded protein andfunction. As the next-generation DNA sequencing platforms have becomewidely available and provide us the technical conditions and experimentalplatform to detect the underlying genetic cause. In this study, a designedpanel which is related to short diseases (27genes of congenitalhypothyroidism included) was used to detect23primary congenitalhypothyroidism patients. It turns out eight patients were detected withpossible genetic mutations. Those are one case with compoundheterozygosis mutation in TSHR gene c.394G>C (p.Gly132Arg) andc.1803T>A (p.Tyr601*); two cases with compound heterozygosis mutationin SLC5A5gene c.1021G>A (p.Gly341Arg) and c.1330-2A>C; one casewith compound heterozygosis mutation in TG gene c.727C>T(p.Arg243Trp) and c.6200-2A>G; one case with compound heterozygosismutation in DUOX2gene c.3329G>A (p.Arg1110Gln) and c.1027G>C(p.Gly343Arg); one case with heterozygosis mutation in NKX2-1genec.913C>T (p.Pro305Ser); two cases with heterozygosis mutation inNKX2-1gene c.703G>T (p.Val235Phe). After data filtering, mapping and variant detection, those genes were suspected to be the virulence genes. Toconfirm the mutations, Sanger sequencing of the8patients and theirparents were performed. In conclusion, there are gene mutations in thePatients with congenital hypothyroidism by Target Next-GenerationSequencing and it has predictive value for next generation prepotency.