Endocrine Abstracts

Background

DUOXA2 mutations in patients with congenital hypothyroidism (CH) was first described in 2008 as rare cause of CH. mRNA of DUOXA2 is expressed predominantly in thyroid and less in salivary glands. Human DUOXA2 gene is located on 15q21.1 and inherited in an autosomal recessive pattern. In most cases DUOXA2 gene mutations were described in patients with thyroid dishormonogenesis. Last investigations conferred DUOXA2 susceptibility to thyroid dysgenesis (TD).

Methods

Twenty one genes related to CH (AITD3, DUOX2, DUOXA2, DUOX1, FOXE1, FOXE2, GLIS3, GLIS4, GNAS, IYD, NKX2–1, NKX2–5, PAX8, SECISBP2, SLC16A2, SLC26A4, SLC5A5, THRA, THRB, TPO, AITD4) were sequenced and screened for variations by next-generation sequencing (NGS) in this family.

Case report

1 patient: adult 24 yrs. female with congenital hypothyroidism caused by thyroid dysgenesis. Neonatal TSH was 173.7 mU/l, serum TSH – 301.1 mU/l. She was followed in endocrine research center from infancy. Ultrasound imagines did not reveal thyroid tissue, thyroglobulin was low (less 0.1 ng/ml). She gave birth to a baby at 24. The pregnancy proceeded normally and the delivery was without complications. 2 patient (proband): daughter of patient 1, five weeks aged, with no signs of hypothyroidism in neonatal period. Neonatal screening conducted on the third day of life. TSH was slightly increased to 9.5 mU/l and 22 mU/l on 3d and 14th day, respectively. Before onset of therapy, serum TSH was increased to 78 mU/l and fT4 decreased to 7.5 pmol/l, serum thyroglobulin level was high as 125 ng/ml (reference range 0–50). Ultrasound imaging did not show thyroid gland in typical position of the neck, during following investigation thyroid tissue was found near the hyoid bone. Heterozygous novel variant mutation c.552A > G:p.L184L in DUOXA2 (NM 207581.4) was detected in mother and proband with thyroid dysgenesis.

Conclusions

We report a novel heterozygous DUOXA2 mutation in the family with thyroid dysgenesis (mother and daughter). Homozygous DUOXA2 mutations described in patients with thyroid dyshormonogenesis. However last investigations revealed heterozygous mutations in DUOXA2 gene in TD patients. The significance of our heterozygous mutation remains unknown and require further researching.