Genetic analysis of TPO, DUOX2 and DUOXA2 genes in children with permanent congenital hypothyroidism suspected dyshormonogenesis
10.3760/cma.j.issn.0578-1310.2017.03.009
- VernacularTitle: 疑似甲状腺素合成障碍性永久性先天性甲状腺功能减低症患儿TPO、DUOX2及DUOXA2基因突变分析
- Author:
Yonglan HUANG
1
;
Minyi TAN
;
Xiang JIANG
;
Bei LI
;
Qianyu CHEN
;
Xuefang JIA
;
Chengfang TANG
;
Jilian LIU
;
Li LIU
Author Information
1. Department of Guangzhou Newborn Screening Center, Guangzhou Women and Children′s Medical Center, Guangzhou 510180, China
- Publication Type:Clinical Trail
- Keywords:
Congenital hypothyroidism;
Gene;
Mutation
- From:
Chinese Journal of Pediatrics
2017;55(3):210-214
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the TPO, DUOX2 and DUOXA2 genotypes and phenotypes of children with permanent congenital hypothyroidism(PCH) suspected dyshormonogenesis in Guangzhou, identified and treated at Guangzhou Newborn Screening Center. Six of them were born between 2011 and 2012.
Method:Retrospectively analyzed the clinical data of 9 children with PCH suspected dyshormonogenesis. Genetic analysis of TPO, DUOX2 and DUOXA2 genes were performed with Sanger sequencing.
Result:Of the 9 patients, four were identified variants in TPO gene including three cases with biallelic variants and one case with monoallelic variant. Novel c. 1784G>C( p. R595T) variant in TPO was predicted to be damaging by SIFT and PolyPhen-2. Four patients harbored monoallelic known variants in DUOX2 gene and the other one harbored heterozygous known mutation c. 738C>G(p.Y246X) in DUOXA2 gene.Two adolescent patients with biallelic variants in TPO gene showed classical PCH phenotypes with thyroid goiter or nodules. The six patients with monoallelic variant in TPO, DUOX2 or DUOXA2 presented variable phenotypes. Among the 433 578 newborns in the 2011-2012 cohort, there were 156 cases of CH. Six of these cases were PCH suspected dyshormonogenesis, among which 1 case was confirmed TPO biallelic variants and 5 cases were monoallelic variants of TPO, DUOX2, or DUOXA2 genes.
Conclusion:TPO and DUOX2 variants are the common molecular pathogenesis in children with PCH suspected dyshormonogenesis. Monoallelic variants in TPO, DUOX2 or DUOXA2 are associated with PCH and showed wide variability in their phenotypes. The novel variant p. R595T in TPO is probably a pathologic variant. The prevalence of PCH caused by TPO gene defects is rare in Guangzhou.
