Pathogenic <i>TSHR</i> variants in children with thyroid dysgenesis

• DOI: 10.14341/probl13210
• Publication Date: 2023-02-27T05:58:30Z
• Authors: E. V. Shreder; T. A. Vadina; E. N. Solodovnikova; V. V. Zakharova; M. V. Degtyarev; M. B. Konyukhova; N. V. Sergeeva; O. B. Bezlepkina
• Keywords: Dysgenesis; Congenital hypothyroidism; Aplasia

BACKGROUND : Loss-of-function mutations in the TSH receptor gene (TSHR) (NP_000360.2) are potential causes of thyroid dysgenesis patients with congenital hypothyroidism. Heterozygous variants TSHR lead to partial resistance TSH, homozygous and compound heterozygous have been shown cause CH due hypoplasia or resistance. Recently more articles this field appeared international literature sources, while local publications limited. The studies necessary understand etiology, pathogenesis disease, improve management these patients. AIM To assess frequency incidence pathogenic children dysgenesis. study inheritance phenotypic patterns families. MATERIALS AND METHODS In single-center interventional one-stage non-comparative a group was examined. underwent neck ultrasound radionuclide imaging. examination performed 14 days after hormone replacement therapy suspension prior its initiation. structure estimated, genetic testing for using NGS method. RESULTS included 95 primary (75 girls; 20 boys). patients’ median age at time 6.2 years [4.5; 8.9], level neonatal 157.5 mU/l [60.9; 257.2]. Ectopic found 52% children, aplasia 36%, hemiagenesis 10% 2%, respectively. 5.4% cases (in 5 out patients), different were detected. Two had p.R450H p.D487N gene, two p.S49Afs * 9 variant, one child (p.A485D p.R450H). According imaging, all varying severity. Three scintigraphy, which revealed decreased 99m Тc pertechnetate uptake (0.3–0.9%). CONCLUSION our study, 5.3%. Our analysis uncovered previously undescribed variants. Genetic may be able help making diagnosis, patient’s management, counseling.