Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families.

Full Abstract

Generalized resistance to thyroid hormone (GRTH) is a syndrome of variable reduction of tissue responsiveness to thyroid hormone. 28 different point mutations in the human thyroid hormone receptor beta (TR beta) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TR beta (codons 310-347 and 417-453). We now report point mutations in the TR beta gene of six additional families with GRTH and show that three mutations occurred each in three families with GRTH, and that three other mutations were each present in two families. In 11 of these 15 families, lack of a common ancestor could be confirmed by genetic analysis. 28 of the 38 point mutations so far identified, including all those occurring in more than one family, are located in cytosine-guanine-rich areas of the TR beta gene. Differences in clinical and laboratory findings in unrelated families harboring the same TR beta mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action.

Author information

Author/s: Weiss, R E (RE); Weinberg, M (M); Refetoff, S (S);

Affiliation: Department of Medicine, University of Chicago, Illinois 60637-1470.

Grants: DK-02081 (Agency:NIDDK NIH HHS) ; DK-15070 (Agency:NIDDK NIH HHS) ; RR-00055 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of clinical investigation (J Clin Invest), published in UNITED STATES. (Language: eng)

Reference: 1993-Jun; vol 91 (issue 6) : pp 2408-15

Dates: Created 1993/07/21; Completed 1993/07/21; Revised 2008/11/20;

PMID: 8514853, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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