Author(s): Wenxiu Han, Hongwei Zang, Yucui Zang, Shiguo Liu, Yinlin Ge
The objective of this research is to study the types and characteristics of DEHAL1 gene mutation in patients with congenital hypothyroidism (CH) and thyroid goiter from Shandong Province, which can provide some evidence for gene diagnosis of CH. 47 cases of patients who were diagnosed as CH combined with thyroid goiter by neonatal screening and 100 normal controls were selected as subjects and their genome DNA were extracted. All the exons were amplified by polymerase chain reaction (PCR) and PCR products were sequenced by direct sequencing (Sanger sequencing). DNA sequencing results were compared to the DEHAL1 gene reference sequence to see whether there was mutation, and χ2 test was used on the gene frequency of discovered Single Nucleotide Polymorphisms (SNP). The results showed that no DEHAL1 gene mutation was found in 60 cases of CH with thyroid goiter patients and 100 normal controls, however, two SNPs were found(rs672766, IVS3+129C>T; rs2076292, IVS3+142C>T) in intron region. There was no significant difference between the SNP rate in CH patients and normal controls (P > 0.05). It can be concluded that DEHAL1 gene mutation rate is very low which may not be the main factor leading to the congenital hypothyroidism (CH) with thyroid goiter in Shandong Province, China.
Congenital hypothyroidism, DEHAL1, Thyroid goiter, Mutation, Child
- . Burniat A, Pirson I, Vilain C, et al. Iodotyrosine deiodinase defect identified via genome-wide approach[J]. J Clin Endocrinol Metab, 2012,97(7):E1276-1283.
- . Chua C, Gurnurkar S, Rodriguez-Prado Y, et al. Prolonged ileus in an infant presenting with primary congenital hypothyroidism[J]. Case Rep Pediatr, 2015,2015:584735.
- . Targovnik HM. Importance of molecular genetic analysis in the diagnosis and classification of congenital hypothyroidism[J]. Endocrine, 2014,45(2):163-164.
- . Bas VN, Cangul H, Agladioglu SY, et al. Mild and severe congenital primary hypothyroidism in two patients by thyrotropin receptor (TSHR) gene mutation[J]. J Pediatr Endocrinol Metab, 2012,25(11-12):1153-1156.
- . Nakamura K, Sekijima Y, Nagamatsu K, et al. A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea[J]. J Neurol Sci, 2012,313(1-2):189-192.
- . Carvalho A, Hermanns P, Rodrigues AL, et al. A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract[J]. Thyroid, 2013,23(9):1074-1078.
- . Teissier R, Guillot L, Carre A, et al. Multiplex Ligation-dependent Probe Amplification improves the detection rate of NKX2.1 mutations in patients affected by brain-lung-thyroid syndrome[J]. Horm Res Paediatr, 2012,77(3):146-151.
- . Castanet M, Polak M. Spectrum of Human Foxe1/TTF2 Mutations[J]. Horm Res Paediatr, 2010,73(6):423-429.
- . Targovnik HM, Esperante SA, Rivolta CM. Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations[J]. Mol Cell Endocrinol, 2010,322(1-2):44-55.
- . Moreno JC, Visser TJ. Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations[J]. Mol Cell Endocrinol, 2010,322(1-2):91-98.
- . Targovnik HM, Edouard T, Varela V, et al. Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: identification a cryptic donor splice site in the exon 19[J]. Mol Cell Endocrinol, 2012,348(1):313-321.
- . Altmann K, Hermanns P, Muhlenberg R, et al. Congenital goitrous primary hypothyroidism in two German families caused by novel thyroid peroxidase (TPO) gene mutations[J]. Exp Clin Endocrinol Diabetes, 2013,121(6):343-346.
- . Yi RH, Zhu WB, Yang LY, et al. A novel dual oxidase maturation factor 2 gene mutation for congenital hypothyroidism[J]. Int J Mol Med, 2013,31(2):467-470.
- . Kasahara T, Narumi S, Okasora K, et al. Delayed onset congenital hypothyroidism in a patient with DUOX2 mutations and maternal iodine excess[J]. Am J Med Genet A, 2013,161a(1):214-217.
- . Mostofizade N, Nikpour P, Javanmard SH, et al. The G395R Mutation of the Sodium/Iodide Symporter (NIS) Gene in Patients with Dyshormonogenetic Congenital Hypothyroidism[J]. Int J Prev Med, 2013,4(1):57-62.
- . Kopp P. Mutations in the Pendred Syndrome (PDS/SLC26A) gene: an increasingly complex phenotypic spectrum from goiter to thyroid hypoplasia[J]. J Clin Endocrinol Metab, 2014,99(1):67-69.
- . Afink G, Kulik W, Overmars H, et al. Molecular characterization of iodotyrosine dehalogenase deficiency in patients with hypothyroidism[J]. J Clin Endocrinol Metab, 2008,93(12):4894-4901.
- . Moreno JC, Pauws E, van Kampen AH, et al. Cloning of tissue-specific genes using serial analysis of gene expression and a novel computational substraction approach[J]. Genomics, 2001,75(1-3):70-76.
- . Moreno JC. Identification of novel genes involved in congenital hypothyroidism using serial analysis of gene expression[J]. Horm Res, 2003,60 Suppl 3:96-102.
- . Gnidehou S, Caillou B, Talbot M, et al. Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site[J]. FASEB J, 2004,18(13):1574-1576.
- . Moreno JC, Klootwijk W, van Toor H, et al. Mutations in the iodotyrosine deiodinase gene and hypothyroidism[J]. N Engl J Med, 2008,358(17):1811-1818.
- . Iglesias A, Garcia-Nimo L, Cocho de Juan JA, et al. Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects[J]. Best Pract Res Clin Endocrinol Metab, 2014,28(2):151-159.
- . Iglesias A, Anyane-Yeboa K, Wynn J, et al. The usefulness of whole-exome sequencing in routine clinical practice[J]. Genet Med, 2014,16(12):922-931.
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