Mutation screening of the TSHR gene in 220 Chinese patients with congenital hypothyroidism

Background Defects in the human thyroid stimulating hormone receptor (TSHR) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and analyze the relationships between TSHR phenotypes and clinical phenotypes. Methods 220 patients with primary CH were screened for TSHR mutations by performing next-generation sequencing. All the exons and exon–intron boundaries of TSHR were analyzed. The function of 8 mutants in TSHR were further investigated in vitro. Results Among 220 patients with CH, 15 distinct TSHR mutations were identified in 13 patients (5.91%, 13/220, including our previous reported 110 patients, carried with 10 mutations in 8 patients). We found five distinct mutations in the additional cohort of 110 CH patients and identified 7 mutations (including a novel mutation, p.S567R) were loss-of-function mutations. Conclusion Our study indicated that the prevalence of TSHR mutations was 5.91% among studied Chinese patients with CH. One novel TSHR variant was found and four genetic alterations revealed important role of the Ile216, Ala275, Asn372, Ser567 residues in signaling.