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 language | English (US) |
|---|---|
| Pages (from-to) | 2408-2415 |
| Number of pages | 8 |
| Journal | Journal of Clinical Investigation |
| Volume | 91 |
| Issue number | 6 |
| State | Published - 1993 |
| Externally published | Yes |
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Keywords
- allele specific amplification
- dinucleotide repeat polymorphism
- free thyroxine
- thyrotropin
ASJC Scopus subject areas
- Medicine(all)
Cite this
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. / Weiss, Roy E; Weinberg, M.; Refetoff, S.
In: Journal of Clinical Investigation, Vol. 91, No. 6, 1993, p. 2408-2415.Research output: Contribution to journal › Article
}
TY - JOUR
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
Y1 - 1993
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.
KW - allele specific amplification
KW - dinucleotide repeat polymorphism
KW - free thyroxine
KW - thyrotropin
UR - http://www.scopus.com/inward/record.url?scp=0027281426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027281426&partnerID=8YFLogxK
M3 - Article
C2 - 8514853
AN - SCOPUS:0027281426
VL - 91
SP - 2408
EP - 2415
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 6
ER -