A mutation in the thyroid hormone receptor alpha gene.
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Bochukova E, Schoenmakers N, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, Henning E, Reinemund J, Gevers E, Sarri M, Downes K, Offiah A, Albanese A, Halsall D, Schwabe JW, Bain M, Lindley K, Muntoni F, Vargha-Khadem F, Dattani M, Farooqi IS, Gurnell M, Chatterjee K
A mutation in the thyroid hormone receptor alpha gene.
N Engl J Med. 2012 Jan 19;366(3):243-9. doi: 10.1056/NEJMoa1110296. Epub 2011 Dec 14.
- PubMed ID
- 22168587 [ View in PubMed]
- Abstract
Thyroid hormones exert their effects through alpha (TRalpha1) and beta (TRbeta1 and TRbeta2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner. Our observations are consistent with defective human TRalpha-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.