Elena Bochukova

Publications (1)53.3 Total impact

• Article: A mutation in the thyroid hormone receptor alpha gene.

  Elena Bochukova, Nadia Schoenmakers, Maura Agostini, Erik Schoenmakers, Odelia Rajanayagam, Julia M Keogh, Elana Henning, Jana Reinemund, Evelien Gevers, Margarita Sarri, [......], David Halsall, John W R Schwabe, Murray Bain, Keith Lindley, Francesco Muntoni, Faraneh Vargha-Khadem, Mehul Dattani, I Sadaf Farooqi, Mark Gurnell, Krishna Chatterjee
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  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.
  New England Journal of Medicine 12/2011; 366(3):243-9. · 53.30 Impact Factor