DUOX2 hotspots variants and outcomes of patients with congenital hypothyroidism suspected thyroid dyshormonogenesis / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate prospectively molecular and clinical characteristics of infants with congenital hypothyroidism (CH) caused by DUOX2 mutations in Guangzhou.Methods A population-based cohort of 83patients with CH were recruited based on newborn screening results among 108 899 newborns who were born in Guangzhou between April 1 and September 30 in 2015.Genetic analysis of DUOX2 hotspots(including 11 exons) by PCR-direct sequencing was performed in 52 patients with suspected thyroid dyshormonogenesis (SDH) according to thyroid ultrasound at diagnosis.All the patients were followed up for 3 years.The data of this cohort study(prevalence of CH,detection rate of DUOX2,clinical features) were compared with those of 96 patients with SDH in 2011-2012.Results (1) The incidence of CH in 2015 was 1 ∶ 1 312,and 73.5％ (61/83 cases) of CH patients were classified as SDH.Compared with those founded in 2011-2012,the incidence of CH was increased (1 ∶ 1 312 vs.1 ∶ 2 779),and the difference was significant (P ＜ 0.001),while the frequency of SDH was not different significantly (73.5 ％ vs.76.6％,P =0.593).(2) There were 27 cases (51.9％) with SDH detected DUOX2 hotspots variants,including 6 cases with biallelic variants,21 cases with monoallelic variants,and 1 possible new pathogenic variant p.S1091F.The p.K530X was the most common mutation accounting for 51.5％ (17/33 cases) detected allelic and involving in 16 cases (30.8％) with SDH.Novel p.S1091F variant was probably damaging variant.Both detected rate and spectrum of DUOX2 variant were not significantly different compared with those in 2011-2012 (all P ＞ 0.05).(3) There were no significant differences in the levels of thyrotropin (bsTSH),serum TSH (sTSH),free thyroxine (FT4) and thyroglobulin in neonates with dry blood spot at diagnosis between children with DUOX2 and without DUOX2 variants cases (all P ＞ 0.05).Among 27 cases,24 (88.9％) patients with DUOX2 mutation were transient CH,and 3 cases were permanent CH.Conclusions The incidence of CH was increased in last few years in Guangzhou.Most of them were SDH,and 51.9％ of SDH cases had DUOX2 hotspots variants.Temporary CH is the main clinical outcome.The p.K530X was the most common mutation in this cohort population.