Open AccessVery Severe Resistance to Thyroid Hormone β in One of Three Affected Members of a Family with a Novel Mutation in the THRB Gene
Author(s) -
Haruki Fujisawa,
Julie Gagné,
Alexandra M. Dumitrescu,
Samuel Refetoff
Publication year - 2019
Publication title -
thyroid
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.918
H-Index - 142
eISSN - 1557-9077
pISSN - 1050-7256
DOI - 10.1089/thy.2019.0095
Subject(s) - proband , mutation , triiodothyronine , thyroid , gene , endocrinology , medicine , mutant , phenotype , hormone , biology , allele , genetics , point mutation
A 13-year-old female with a novel THRB gene mutation (c.1033G>T, p.G345C) presented with 3- to 6-fold higher serum iodothyronine levels and more severe clinical manifestation than 2 other family members carrying the same mutation. The leukocytes of the proband expressed both wild-type and mutant THRB mRNAs, excluding the possibility of a partial deletion of the allele not carrying the mutation. The proband's fibroblasts showed reduced responsiveness to triiodothyronine compared with those of another affected family member. The more severe clinical and biochemical phenotype suggest a modifier-mediated worsening of the resistance to thyroid hormone.