Detection of the R450H mutation in the TSHR gene in neonates diagnosed with congenital primary hypothyroidism through neonatal screening
- VernacularTitle:Нярайн скрининг шинжилгээгээр төрөлхийн анхдагч гипотиреоз оношлогдсон дээжинд TSHR генийн R450H мутацийг илрүүлсэн дүн
- Author:
Nomindelger T
1
;
Nomunbileg M
1
;
Elberelt U
2
;
Erdenetuya G
3
;
Munkhtsetseg B
1
Author Information
1. Department of Molecular biology and Genetics, School of Bio-Medicine, MNUMS
2. Institute of Biomedical sciences, MNUMS
3. Department of Pediatrics, School of Medicine, MNUMS
- Publication Type:Journal Article
- Keywords:
Congenital hypothyroidism;
Dried blood spot;
TSHR Gene;
p.R450H mutation;
Fragment Length Polymorphism Analysis
- From:
Mongolian Journal of Health Sciences
2026;95(5):131-135
- CountryMongolia
- Language:Mongolian
-
Abstract:
Background:Congenital hypothyroidism (CH) is a condition characterized by a decrease in the amount of thyroid hormones in the blood or a complete lack of thyroid function due to a decrease in the amount of thyroid hormones in the blood or a complete lack of thyroid hormones. CH occurs in 1 per 3000-4000 live births worldwide. The clinical symptoms of CH are initially subtle, usually appearing within a month of birth, and if diagnosis and treatment are delayed, it can lead to physical and mental developmental delays and eventual disability. The cause of the disease is not fully known, but it is believed to be influenced by maternal iodine deficiency and mutations in genes responsible for neonatal thyroid development (TSHR, PAX8, NKX2-1, and FOXE1 transcription factors). More than 40 types of TSHR gene mutations are causing CH. Studies conducted in Japan, China, and Taiwan have shown that the p.R450H mutation in the TSHR gene is a risk factor for CH. In Mongolia, a newborn screening analysis of congenital hypothyroidism revealed a rate of 1 case per 2091 live births in 2021, which is higher than the global average. However, there is a lack of molecular genetic research on this condition in the country.
Aim:To identify of p.R450H mutation in the TSHR gene among neonates diagnosed with congenital hypothyroidism through neonatal screening
Materials and Methods:The study used dried blood spots from 17 children diagnosed with congenital hypothyroidism at Mongolian-Japanese University hospital and Central Hospital of MNUMS from 2012 to 2024. To identify an optimal method for DNA extraction from dried blood samples, we evaluated five different protocols. DNA was extracted using the method that yielded the highest quantity and purity, and the TSHR gene was subsequently amplified by PCR. Detecting the p.R450H mutation of the TSHR gene, the PCR product was cut with Faul restriction enzyme and the results were evaluated by gel electrophoresis.
Results:In our study, DNA isolation from dried blood using methods 1 and 2 had high yield and purity, so we isolated DNA from samples of 17 children diagnosed with congenital primary hypothyroidism and amplified the TSHR gene by PCR. When the PCR products were run through gel electrophoresis, 14 samples were amplified by PCR. After that, the genotype of the p.R450H mutation of the TSHR gene was determined by fragment length polymorphism analysis, and 11 (78.6%) samples were found to have the G/G genotype, 2 (14.3%) samples were found to have the G/A genotype, and 1 (7.1%) sample was found to have the A/A genotype, respectively.
Conclusion:Among children with congenital hypothyroidism diagnosed through newborn screening test between 2012 and 2024, the p.R450H homozygous and heterozygous mutation in the TSHR gene was 21.4%.
- Full text:2026100121162812838Нярайн скрининг шинжилгээгээр.pdf
