Thyrotropin Receptor and Thyroid Transcription Factor-1 Genes Variant in Chinese Children with Congenital Hypothyroidism

Abstract

Abstract. The aim of the present study was to investigate the mutation/variant of thyrotropin receptor (TSHR) and thyroid transcription factor-1 (TTF-1) genes in Chinese children with congenital hypothyroidism (CH). Seventy-nine and forty-nine Chinese children with CH were enrolled for molecular analysis of the TSHR gene and TTF-1 gene, respectively. One hundred normal children were evaluated as control. The coding regions of TSHR and TTF-1 genes were amplified by polymerase chain reaction and sequenced. Sequencing of the TSHR gene revealed a compound heterozygous variants (Pro52Thr/Val689Gly) and a heterozygous variant (Gly245Ser) in 2 of 79 patients. In 30 patients and 33 controls the normal cytosine at position 2181 in exon 10 of TSHR gene was replaced by a guanine， resulting in the replacement of Asp 727 by Glu. In 47 patients and 50 controls, the normal thymidine at position 561 in exon 7 of TSHR gene was replaced by a cytosine. This substitution did not change the amino acid in position 187. Sequencing of the TTF-1 gene revealed no mutation or polymorphism in 49 patients and 100 controls. In conclusion, three heterozygous variants (Pro52Thr, Gly245Ser, Val689Gly) of TSHR gene were firstly detected in Chinese children with CH. There were polymorphisms in exon 10 at nucleotide 2181 (C/G) and in exon 7 at nucleotide 561 (T/C) in TSHR gene. No mutation or polymorphism was detected in the coding region of TTF-1 gene. The mutation/variant of TSHR and TTF-1 genes is relatively rare in Chinese children with CH.

High Frequency of D727E Polymorphisms in Exon 10 of the TSHR Gene in Brazilian Patients with Congenital Hypothyroidism

“…However, Fisher's exact test was significant for A459A polymorphism (P=0,0264) ( Table 01). The results of our study did not show any association between the D727E polymorphism and primary CH, and are consistent with other studies [19][20][21] . Gabriel et al (1999) suggested that the D727E polymorphism is important in the pathogenesis of multinodular toxic goiter.…”

“…The frequency of the D727E polymorphism found in this study (10%) is the second highest reported in patients with HC, lower only than that reported by Yuan et al, 2008. When compared with other reports (see studies 11,17,19,21,22,26-29 in Table 02), the frequency of the D727E polymorphism recorded in our study is still relatively high.…”

Current loss-of-function mutations in the thyrotropin receptor gene: when to investigate, clinical effects, and treatment

“…To date, more than 60 mutations in the TSHR gene have been described in association with different degrees of TSH resistance (Table 2, continued 1, continued 2,) (4,5,6,7,8,9,10,11,12,13,14,15,16,17,18, 19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36, 37,38,39,40,41,42). The mutations are all point mutations, such as base substitutions and small deletions/insertions that cause missense (the most frequent), nonsense and frame shift mutations.…”

Consecutive Mutational Events in a TSHR Allele of Arab Families with Resistance to Thyroid Stimulating Hormone

“…Data on the prevalence of inactivating mutations in the TSHR gene in patients with congenital hyperthyroidism or nonautoimmune hyperthyrotropinemia are variable, from 2% to 40% depending on selection criteria of the population studied (9,(15)(16)(17)(18)(19)(20)(21)(22). Population-based genetic study in Japan showed that the TSHR mutations are not an uncommon cause of RTSH (4).…”