A novel dual oxidase maturation factor 2 gene mutation for congenital hypothyroidism

Abstract

Congenital hypothyroidism (CH) is caused by thyroid hormone deficiency present at birth. DUOXA2 (dual oxidase maturation factor 2) is one of the prerequisites for thyroid hormone synthesis. The present study explored the novel mutations of DUOXA2 in CH patients. Genomic DNA was extracted from peripheral blood of 47 unrelated CH patients, their family members and 100 healthy controls. All 6 exons and their flanking sequences of the DUOXA2 gene were PCR amplified and sequenced. Sequencing results were compared with the standard. Compound heterozygosity with DUOXA2 gene mutations at c.413-414insA (Y138X) and c.738C>G (Y246X) was identified in one patient, and absent in 100 healthy controls. Among them, the c.413‑414insA (Y138X) mutation was a novel one. The patient with the c.413-414insA (Y138X) mutation had mild CH symptoms. This study is the first to report a novel c.413-414insA (Y138X) mutation for CH, thereby expanding the mutational spectrum of the DUOXA2 gene.

Fetal Goitrous Hypothyroidism and Polyhydramnios in a Patient with Compound Heterozygous <b><i>DUOXA2</i></b> Mutations

“…Next-generation sequencing-based comprehensive mutation screening showed that the patient was compound heterozygous for 2 previously reported nonsense DUOXA2 mutations (p.[Tyr138*] [15] and p.[Tyr246*] [7]). The parents harbored 1 mutation each in a heterozygous state (Fig.…”

Homozygous <i>DUOXA2</i> mutation (p.Tyr138^*) in a girl with congenital hypothyroidism and her apparently unaffected brother: Case report and review of the literature

“…Nonetheless, DUOX1 (and possibly DUOXA1) could have a minor role in H 2 O 2 production in the thyroid, because CH in biallelic DUOX2 mutation carriers is often transient [6], and those mutation carriers produce thyroid hormones presumably via DUOX1 in the post-infantile period [7]. As for DUOXA2 mutation carriers, only four unrelated CH patients have been reported [5,[8][9][10], and thus the phenotypic spectrum remains to be established. Here, we report the fifth DUOXA2 mutation-carrying CH patients, whose brother also had the identical homozygous mutation but did not have CH.…”

“…Next generation sequencing-based comprehensive genetic analysis of the proband led us to identify a homozygous nonsense DUOXA2 mutation (c.413dupA, p.Tyr138*) that had been previously described [9]. No mutation was found in the other sequenced genes.…”

“…In the literature, four CH patients with biallelic DUOXA2 mutations were found [5,[8][9][10], and clinical information was available in three out of the four published cases (Table 1) [5,8,10]. Blood-spot TSH levels at newborn screening ranged from 48 to 135 mU/L, and serum TSH levels at the first medical examination ranged from 12 to 151 mU/L.…”

Study on DEHAL1 Mutations in Patients with Congenital Hypothyroidism and Thyroid Goiter

“…15%-20% of CH patients with thyroid dyshormonogenesis combined with thyroid goiter [1] is inherited as an autosomal recessive trait [10] . Genetic defects of enzymes in the thyroid hormone synthesis pathway, such as DEHAL1 [11] , thyroglobulin (TG) [12] , thyroid peroxidase (TPO) [13] , dual oxidase 2 maturation factor (DUOXA2) [14] , dual oxidase 2 (DUOX2) [15] , sodium-iodide symporter (NIS) [16] and Pendred syndrom (PDS) [17] , can cause thyroid dyshormonogenesis.…”