Abstract
BackgroundHashimoto’s thyroiditis is a complex autoimmune thyroid disease, the onset of which is associated with environmental exposures and specific susceptibility genes. Its incidence in females is higher than its incidence in males. Thus far, although some susceptibility loci have been elaborated, including PTPN22, FOXP3, and CD25, the aetiology and pathogenesis of Hashimoto’s thyroiditis remains unclear.MethodsFour affected members from a Chinese family with Hashimoto’s thyroiditis were selected for whole-exome sequencing. Missense, nonsense, frameshift, or splicing-site variants shared by all affected members were identified after frequency filtering against public and internal exome databases. Segregation analysis was performed by Sanger sequencing among all members with available DNA.ResultsWe identified a missense mutation in PTPN22 (NM_015967.5; c. 77A > G; p.Asn26Ser) using whole-exome sequencing. PTPN22 is a known susceptibility gene associated with increased risks of multiple autoimmune diseases. Cosegregation analysis confirmed that all patients in this family, all of whom were female, carried the mutation. All public and private databases showed that the missense mutation was extremely rare.ConclusionsWe found a missense mutation in PTPN22 in a Chinese HT pedigree using whole-exome sequencing. Our study, for the first time, linked a rare variant of PTPN22 to Hashimoto’s thyroiditis, providing further evidence of the disease-causing or susceptibility role of PTPN22 in autoimmune thyroid disease. Functional studies regarding the effects of this variant on thyroid autoimmunity and thyroid function are warranted.
Highlights
Hashimoto’s thyroiditis is a complex autoimmune thyroid disease, the onset of which is associated with environmental exposures and specific susceptibility genes
Autoimmune thyroid disease (AITD) constitutes a complex class of diseases, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT); these are associated with interactions of specific susceptibility genes and environmental exposures [1, 2]
Thyroid function tests showed that she had an elevated thyroid peroxidase autoantibody (TPOAb) level (244 IU/ml, normal range: 0–34.0 IU/ml) and an elevated thyroid stimulating hormone (TSH) level (5.37 mIU/L, normal range: 0.372–4.94 mIU/L)
Summary
Hashimoto’s thyroiditis is a complex autoimmune thyroid disease, the onset of which is associated with environmental exposures and specific susceptibility genes. Autoimmune thyroid disease (AITD) constitutes a complex class of diseases, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT); these are associated with interactions of specific susceptibility genes and environmental exposures [1, 2]. Both GD, manifested as hyperthyroidism, and HT, manifested as hypothyroidism, exhibit common characteristics of the production of thyroid autoantibodies and the invasion of thyroid lymphocytes. An A/C polymorphism at − 3279 has been associated with the development of therapeutic resistance in patients with GD, whereas the CC genotype at − 2383 has been associated with severe HT [10] Taken together, these prior studies demonstrate that the FOXP3 polymorphism is associated with AITD. Several other susceptible loci have been associated with AITD, including FCRL3 (Fc receptor-like 3), RNASET2 (ribonuclease T2), SCGB3A2 (secretoglobin, family 3A member 2) [6, 11,12,13,14]
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