Ann Pediatr Endocrinol Metab.  2020 Dec;25(4):282-286. 10.6065/apem.2040076.038.

An A627V-activating mutation in the thyroid-stimulating hormone receptor gene in familial nonautoimmune hyperthyroidism

• Shin JH
• Seo GH
• Oh SH
• Chung WY
• Kim HY
• Kim YM
• Bae MH
• Park KH
• Kwak MJ

• KMID: 2510901
• DOI: http://doi.org/10.6065/apem.2040076.038

Abstract

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Keyword

Congenital hyperthyroidism; Nonautoimmune hyperthyroidism; TSHR gene; Whole-exome sequencing

Figure

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  Fig. 1. Follow-up FT4 and TSH values in the patient. FT4, free T4; TSH, thyroid-stimulating hormone.

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  Fig. 2. Electropherograms obtained from Sanger sequencing of the TSHR gene. A novel missense TSHR variant c.1880C>T (A627V) was identified in the proband and his mother (red arrows).

Reference

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