A somatic gain-of-function mutation in the thyrotropin receptor gene producing a toxic adenoma in an infant

Brenda Kohn, Helmut Grasberger, Leslie S. Lam, Alfonso Massimiliano Ferrara, Samuel Refetoff

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Activating mutations of the thyroid stimulating hormone receptor gene (TSHR) are rare in the neonate and in the pediatric population. They are usually present in the germline, and are either inherited or occur de novo. Somatic mutations in TSHR are unusual in the pediatric population. Methods: We describe a nine-month-old infant with thyrotoxicosis who harbored an activating somatic mutation in TSHR that was not present in the germline. Results: As genomic DNA analysis failed to show a TSHR gene mutation, a radioiodide scan was performed to reveal a unilateral localization of uptake suppressing the remaining thyroid tissue. Genomic and complementary DNA analyses of the active thyroid tissue, removed surgically, identified a missense mutation (D633Y) located in the sixth transmembrane domain of the TSHR. The absence of this TSHR mutation in circulating mononuclear cells and in unaffected thyroid tissue confirmed the somatic nature of this genetic alteration. Conclusions: To the authors' knowledge, this is the youngest patient to receive definitive treatment for hyperthyroidism due to an activating mutation of TSHR.

Original languageEnglish (US)
Pages (from-to)187-191
Number of pages5
JournalThyroid
Volume19
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Thyrotropin Receptors
Poisons
Adenoma
Mutation
Genes
Thyroid Gland
Pediatrics
Thyrotoxicosis
Missense Mutation
Hyperthyroidism
Population
Complementary DNA
Newborn Infant
DNA

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A somatic gain-of-function mutation in the thyrotropin receptor gene producing a toxic adenoma in an infant. / Kohn, Brenda; Grasberger, Helmut; Lam, Leslie S.; Ferrara, Alfonso Massimiliano; Refetoff, Samuel.

In: Thyroid, Vol. 19, No. 2, 2009, p. 187-191.

Research output: Contribution to journalArticle

Kohn, Brenda ; Grasberger, Helmut ; Lam, Leslie S. ; Ferrara, Alfonso Massimiliano ; Refetoff, Samuel. / A somatic gain-of-function mutation in the thyrotropin receptor gene producing a toxic adenoma in an infant. In: Thyroid. 2009 ; Vol. 19, No. 2. pp. 187-191.
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