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; Kate Downes; Amaka Offiah; Assunta Albanese; David Halsall; John W.R. Schwabe; Murray Bain; Keith Lindley; Francesco Muntoni; Faraneh Vargha Khadem; Mehul Dattani; I. Sadaf Farooqi; Mark Gurnell; Krishna Chatterjee

doi:10.1056/NEJMoa1110296

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, Kate Downes, Amaka Offiah, Assunta Albanese, David Halsall, John W.R. Schwabe, Murray Bain, Keith Lindley, Francesco Muntoni, Faraneh Vargha Khadem, Mehul DattaniI. Sadaf Farooqi^*, Mark Gurnell, Krishna Chatterjee

^*Corresponding author for this work

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	243-249
Number of pages	7
Journal	New England Journal of Medicine
Volume	366
Issue number	3
DOIs	https://doi.org/10.1056/NEJMoa1110296
Publication status	Published - 19 Jan 2012

ASJC Scopus subject areas

General Medicine

Access to Document

10.1056/NEJMoa1110296

Cite this

Bochukova, E., Schoenmakers, N., Agostini, M., Schoenmakers, E., Rajanayagam, O., Keogh, J. M., Henning, E., Reinemund, J., Gevers, E., Sarri, M., Downes, K., Offiah, A., Albanese, A., Halsall, D., Schwabe, J. W. R., Bain, M., Lindley, K., Muntoni, F., Khadem, F. V., ... Chatterjee, K. (2012). A mutation in the thyroid hormone receptor alpha gene. New England Journal of Medicine, 366(3), 243-249. https://doi.org/10.1056/NEJMoa1110296

@article{b88c637c4a864b719c6e37dff8e4cb12,

title = "A mutation in the thyroid hormone receptor alpha gene",

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.",

author = "Elena Bochukova and Nadia Schoenmakers and Maura Agostini and Erik Schoenmakers and Odelia Rajanayagam and Keogh, \{Julia M.\} and Elana Henning and Jana Reinemund and Evelien Gevers and Margarita Sarri and Kate Downes and Amaka Offiah and Assunta Albanese and David Halsall and Schwabe, \{John W.R.\} and Murray Bain and Keith Lindley and Francesco Muntoni and Khadem, \{Faraneh Vargha\} and Mehul Dattani and Farooqi, \{I. Sadaf\} and Mark Gurnell and Krishna Chatterjee",

year = "2012",

month = jan,

day = "19",

doi = "10.1056/NEJMoa1110296",

language = "English",

volume = "366",

pages = "243--249",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "3",

}

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, JWR, Bain, M, Lindley, K, Muntoni, F, Khadem, FV, Dattani, M, Farooqi, IS, Gurnell, M & Chatterjee, K 2012, 'A mutation in the thyroid hormone receptor alpha gene', New England Journal of Medicine, vol. 366, no. 3, pp. 243-249. https://doi.org/10.1056/NEJMoa1110296

TY - JOUR

T1 - A mutation in the thyroid hormone receptor alpha gene

AU - Bochukova, Elena

AU - Schoenmakers, Nadia

AU - Agostini, Maura

AU - Schoenmakers, Erik

AU - Rajanayagam, Odelia

AU - Keogh, Julia M.

AU - Henning, Elana

AU - Reinemund, Jana

AU - Gevers, Evelien

AU - Sarri, Margarita

AU - Downes, Kate

AU - Offiah, Amaka

AU - Albanese, Assunta

AU - Halsall, David

AU - Schwabe, John W.R.

AU - Bain, Murray

AU - Lindley, Keith

AU - Muntoni, Francesco

AU - Khadem, Faraneh Vargha

AU - Dattani, Mehul

AU - Farooqi, I. Sadaf

AU - Gurnell, Mark

AU - Chatterjee, Krishna

PY - 2012/1/19

Y1 - 2012/1/19

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84856190300

U2 - 10.1056/NEJMoa1110296

DO - 10.1056/NEJMoa1110296

M3 - Article

AN - SCOPUS:84856190300

SN - 0028-4793

VL - 366

SP - 243

EP - 249

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 3

ER -

A mutation in the thyroid hormone receptor alpha gene

Abstract

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this