Display Settings:

Format

Send to:

Choose Destination
N Engl J Med. 2012 Jan 19;366(3):243-9. doi: 10.1056/NEJMoa1110296. Epub 2011 Dec 14.

A mutation in the thyroid hormone receptor alpha gene.

Author information

  • 1University of Cambridge Metabolic Research Laboratories and National Institute for Health Research Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.

Erratum in

  • N Engl J Med. 2012 Oct 11;367(15):1474. Khadem, Faraneh Vargha [corrected to Vargha-Khadem, Faraneh].

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 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 TRα-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.

Comment in

  • [In Process Citation]. [Rev Clin Esp. 2012]
PMID:
22168587
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Write to the Help Desk