S Acar1, S Gürsoy2, G Arslan3, Ö Nalbantoğlu3, F Hazan4, Ö Köprülü3, B Özkaya3, B Özkan3. 1. Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Education and Research Hospital, İsmet Kaptan Mh, Sezer Doğan Sokağı No:11, 35210, Konak/Izmir, Turkey. dr.acarsezer@gmail.com. 2. Division of Pediatric Genetics, Dr. Behçet Uz Children's Education and Research Hospital, Izmir, Turkey. 3. Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Education and Research Hospital, İsmet Kaptan Mh, Sezer Doğan Sokağı No:11, 35210, Konak/Izmir, Turkey. 4. Department of Medical Genetics, Dr. Behçet Uz Children's Education and Research Hospital, Izmir, Turkey.
Abstract
PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.
PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.
Authors: J M Vuissoz; J Deladoëy; A Buyukgebiz; P Cemeroglu; G Gex; S Gallati; P E Mullis Journal: J Clin Endocrinol Metab Date: 2001-09 Impact factor: 5.958