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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.

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.[1]


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