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

Roy E Weiss, M. Weinberg, S. Refetoff

Research output: Contribution to journalArticle

117 Citations (Scopus)

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 (TRβ) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TRβ (codons 310-347 and 417-453). We now report point mutations in the TRβ 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 TRβ gene. Differences in clinical and laboratory findings in unrelated families harboring the same TRβ mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action.

Original languageEnglish (US)
Pages (from-to)2408-2415
Number of pages8
JournalJournal of Clinical Investigation
Volume91
Issue number6
StatePublished - 1993
Externally publishedYes

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Thyroid Hormone Receptors beta
Thyroid Hormone Resistance Syndrome
Cytosine
Guanine
Point Mutation
Mutation
Thyroid Hormones
Genes
Codon

Keywords

  • allele specific amplification
  • dinucleotide repeat polymorphism
  • free thyroxine
  • thyrotropin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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T1 - 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

AU - Weiss, Roy E

AU - Weinberg, M.

AU - Refetoff, S.

PY - 1993

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N2 - 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 (TRβ) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TRβ (codons 310-347 and 417-453). We now report point mutations in the TRβ 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 TRβ gene. Differences in clinical and laboratory findings in unrelated families harboring the same TRβ mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action.

AB - 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 (TRβ) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TRβ (codons 310-347 and 417-453). We now report point mutations in the TRβ 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 TRβ gene. Differences in clinical and laboratory findings in unrelated families harboring the same TRβ mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action.

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KW - dinucleotide repeat polymorphism

KW - free thyroxine

KW - thyrotropin

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