Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis.

Background The abnormal expression of certain transcription factors ( NKX2.1 , FOXE1 , NKX2.5 , and PAX8 ) and thyroid stimulating hormone receptor (TSHR) genes has been associated with athyreosis, which is a form of thyroid dysgenesis (TD). We aimed to identify candidate gene mutations in CH patients with athyreosis and to establish the genotype-phenotype correlations in a Chinese population. Methods The exons and flanking sequences of NKX2.1 , FOXE1 , NKX2.5 , PAX8 , and TSHR were screened by next-generation sequencing and further confirmed by direct Sanger sequencing. The mutation frequencies were calculated and compared against databases. The relationship between genotype and phenotype was also determined. Results Seven variants were detected in TSHR —p.P52T, p.G132R, p.M164K, p.R450H, p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q, p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected in FOXE1 . In addition, one variant (p.N291I) was found in NKX2.5 and two variants (p.A355V and c.-26G > A) were detected in PAX8 . Conclusions Our study indicated that TSHR mutations have phenotypic variability and has further expanded the mutation spectrum of TSHR . We also revealed that the rate of NKX2.1 , FOXE1 , NKX2.5 , and PAX8 mutations were low in patients with CH and athyreosis, in contrast to the higher rate of TSHR mutations. [ABSTRACT FROM AUTHOR]