Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/12318
Title: A mutation in the thyroid hormone receptor alpha gene
Authors: Bochukova, E.
Schoenmakers, N.
Agostini, M.
Schoenmakers, E.
Rajanayagam, O.
Keogh, J. M.
Henning, E.
Reinemund, J.
Halsall, D.
Farooqi, I. S.
Gurnell, M.
Chatterjee, K.
Downes, K.
Offiah, A.
Schwabe, John W. R.
Gevers, E.
Dattani, M.
Sarri, M.
Khadem, F. V.
Lindley, K.
Albanese, A.
Bain, M.
Muntoni, F.
First Published: 19-Jan-2012
Publisher: Massachusetts Medical Society
Citation: New England Journal of Medicine, 2012, 366 (3), pp. 243-249
Abstract: Thyroid hormones exert their effects through alpha (TRα1) and beta (TRβ1 and TRβ2) 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 wholeexome 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 TRα-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.
DOI Link: 10.1056/NEJMoa1110296
ISSN: 0028-4793
eISSN: 1533-4406
Links: http://hdl.handle.net/2381/12318
http://www.nejm.org/doi/full/10.1056/NEJMoa1110296
Type: Journal Article
Rights: Archived with reference to SHERPA/RoMEO and publisher website.
Appears in Collections:Published Articles, Dept. of Biochemistry

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