A new family with an activating mutation (G431S) in the TSH receptor gene: a phenotype discussion and review of the literature

Abstract

Germline nonautoimmune hyperthyroidism due to an activating mutation in the thyroid stimulating hormone receptor gene is an uncommon disease. To date 32 different mutations have been described. The severity of the hyperthyroid symptoms is variable and phenotype differences have been described in subjects harboring the same mutation. This paper describes a family with a mutation in codon 431 of the thyroid stimulating hormone receptor gene. This is the most common activating mutation in the thyroid stimulating hormone receptor gene with total of 13 patients harboring the mutation in four families. The similarities and differences among patients with the mutation in codon 431 are discussed. Furthermore all previously reported activating mutations in the thyroid stimulating hormone receptor gene are reviewed.Electronic supplementary materialThe online version of this article (doi:10.1186/1687-9856-2014-23) contains supplementary material, which is available to authorized users.

Central TSH Dysregulation in a Patient with Familial Non-Autoimmune Autosomal Dominant Hyperthyroidism Due to a Novel Thyroid-Stimulating Hormone Receptor Disease-Causing Variant

“…An exceptional case, having inappropriate TSH response to severe hypothyroidism 14 years after radioiodine therapy, was reported and discussed by Jaesche et al [28]. From previous reports, additional cases of inappropriate TSH response to hypothyroidism [4,29] and persistent suppression of TSH in euthyrotic state [17,[30][31][32] can be deduced. However, there are also reports demonstrating appropriate TSH in relation to normal thyroid hormones or hypothyroidism [26,33].…”

“…Another essential difference between these two entities is that SCNAH usually occurs in younger children and has a more severe course [2,7]. According to available data, there are 29 different TSHR disease-causing variants in families with FNAH and 20 different TSHR disease-causing variants in individuals with SCNAH [17], with a very little overlap of TSHR variants [2].…”

Severe thyrotoxicosis in an infant revealing familial nonautoimmune hyperthyroidism with a novel (C672W) stimulating thyrotropin receptor germline mutation

“…Most activating germline mutations of the TSH receptor gene are located in the cytoplasmic loops and transmembrane domains, and cause nonautoimmune sporadic congenital hyperthyroidism or familial nonautoimmune hyperthyroidism. Since the first case of familial nonautoimmune hyperthyroidism published in 1982 [1], at least 21 different mutations of the TSH receptor gene have been identified as a cause of autosomal dominant nonautoimmune hyperthyroidism in 28 families with more than 122 affected individuals [2][3][4][5][6][7][8][9][10][11][12].…”