ABSTRACT
BACKGROUND: Resistance to thyroid hormone (RTH) is a rare dominantly inherited disorder mainly due to variants in the THRB gene leading to decreased end-organ responsiveness to thyroid hormones. CASE REPORT: Clinical and molecular characteristics of four patients with RTH are described. Four patients with various phenotypes were studied; two prepubertal boys and two adults (one male and one female). Sequencing analysis of the THRB was performed. All individuals had persistently elevated free thyroxine and/or free triiodothyronine associated with non-suppressed thyroid-stimulating hormone (TSH), and all had non-autoimmune goiters of various sizes. In both adults, antithyroid drugs were previously administered without successful suppression of the thyroid hormones. The 27-year-old female had resting tachycardia as the only symptom. The 35-year-old male had a degree of cognitive impairment and was initially diagnosed with atrial fibrillation. The eight-year-old boy was diagnosed with attention deficit disorder and had resting tachycardia. The oldest boy (age nine years) underwent thyroid function tests as a part of the investigation for obesity and learning difficulties. Direct sequencing analysis of the THRB gene showed three previously reported variants: p.His435Leu (c.1304A>T) in the 35-year-old male, p.Pro453Thr (c.1357C>A) in the oldest boy, and p.Arg438Cys (c.1312C>T) variant in the other two patients. CONCLUSIONS: Various phenotypes characterize common variants in the THRB gene, asymptomatic, thyroid hormone deprivation symptoms, or thyroid hormone excess symptoms. RTH should be suspected in both adults and children with elevated thyroid hormones and not suppressed TSH. A prompt molecular diagnosis and genetic counseling could prevent unnecessary tests and inappropriate treatments. HIPPOKRATIA 2019, 23(3): 135-139.
ABSTRACT
Type I diabetes mellitus (T1DM) is an organ-specific autoimmune disorder affecting the insulin-producing pancreatic cells. T1DM genetic association studies have so far revealed the involvement of more than 40 loci, with particularly strong associations for the human leucocyte antigens (HLA). Further to the well-established HLA class II associations, the immunomodulatory elements in the telomeric major histocompatibility complex locus, specifically nonclassical HLA class I, were also associated with T1DM, either in conferring susceptibility or by contributing to the overall pathogenesis. This study investigates the involvement of a 14-bp deletion polymorphism (rs371194629) at the 3' untranslated region of HLA-G in the context of T1DM and age of onset. The frequency of the polymorphism was determined in unrelated T1DM Cypriot patients and findings that emerge from this study show a strong association between the HLA-G 14-bp polymorphism and T1DM with respect to the age of onset. Specifically, the deletion/deletion (DEL/DEL) genotype was found to be associated with an early age of onset (P = 0.001), while the presence of the insertion allele (INS) was associated to a later age of onset (P = 0.0001), portraying a possible dominant effect over the deletion allele, a role in delaying disease onset and an overall involvement of HLA-G in the pathogenesis of type I diabetes mellitus.
