Abstract
Resistance to thyroid hormone (RTH) is a rare disease characterized by goiter and elevated free thyroid hormone (TH) levels in the presence of detectable concentrations of TSH. Most RTH patients harbor mutations in the ligand binding domain (LBD) of thyroid hormone receptor β (TRβ) gene, without a clear correlation between genotype and phenotype. Clinical, biochemical and genetic analyses were performed in several members of one family, because the index case presented with elevated free TH, measurable TSH and no hyperthyroid manifestations, but with a pituitary lesion at MRI. High free TH levels and TSH concentrations in the normal range were found also in 4 relatives. The presence of euthyroidism in all patients together with peripheral parameters of TH action in the normal range led to the diagnosis of generalized RTH (GRTH). In the five affected members, the genetic analysis revealed a novel heterozygous missense mutation at codon 334 (M334T). A different mutation at codon 334 was previously described in association with selective pituitary resistance to thyroid hormone (PRTH). Therefore, we confirm that substitutions at Methionine 334 are critical for the structural integrity of TRβ LBD. The association of different phenotypes with substitutions affecting the same codon is another contribution confirming that RTH phenotype does not generally depend upon the site of the mutation in the LBD of TRβ1.
| Original language | English |
|---|---|
| Journal | Journal of Endocrinological Investigation |
| Volume | 25 |
| Issue number | 2 |
| Publication status | Published - 2002 |
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Keywords
- ACE
- Glycoprotein α-subunit (α-GSU)
- ICTP
- Mutation
- Peripheral parameters
- Pituitary incidentaloma
- RTH
- SHBG
- Thyroid hormone resistance syndrome
- TRβ gene
ASJC Scopus subject areas
- Endocrinology
Cite this
Genetic analyses and evaluation of peripheral parameters of thyroid hormone action for the differential diagnosis of RTH. A novel heterozygous missense mutation (M334T) discovered. / Mannavola, D.; Vannucchi, G.; Fugazzola, L.; Cerutti, N.; Persani, L.; Beck-Peccoz, Paolo.
In: Journal of Endocrinological Investigation, Vol. 25, No. 2, 2002.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic analyses and evaluation of peripheral parameters of thyroid hormone action for the differential diagnosis of RTH. A novel heterozygous missense mutation (M334T) discovered
AU - Mannavola, D.
AU - Vannucchi, G.
AU - Fugazzola, L.
AU - Cerutti, N.
AU - Persani, L.
AU - Beck-Peccoz, Paolo
PY - 2002
Y1 - 2002
N2 - Resistance to thyroid hormone (RTH) is a rare disease characterized by goiter and elevated free thyroid hormone (TH) levels in the presence of detectable concentrations of TSH. Most RTH patients harbor mutations in the ligand binding domain (LBD) of thyroid hormone receptor β (TRβ) gene, without a clear correlation between genotype and phenotype. Clinical, biochemical and genetic analyses were performed in several members of one family, because the index case presented with elevated free TH, measurable TSH and no hyperthyroid manifestations, but with a pituitary lesion at MRI. High free TH levels and TSH concentrations in the normal range were found also in 4 relatives. The presence of euthyroidism in all patients together with peripheral parameters of TH action in the normal range led to the diagnosis of generalized RTH (GRTH). In the five affected members, the genetic analysis revealed a novel heterozygous missense mutation at codon 334 (M334T). A different mutation at codon 334 was previously described in association with selective pituitary resistance to thyroid hormone (PRTH). Therefore, we confirm that substitutions at Methionine 334 are critical for the structural integrity of TRβ LBD. The association of different phenotypes with substitutions affecting the same codon is another contribution confirming that RTH phenotype does not generally depend upon the site of the mutation in the LBD of TRβ1.
AB - Resistance to thyroid hormone (RTH) is a rare disease characterized by goiter and elevated free thyroid hormone (TH) levels in the presence of detectable concentrations of TSH. Most RTH patients harbor mutations in the ligand binding domain (LBD) of thyroid hormone receptor β (TRβ) gene, without a clear correlation between genotype and phenotype. Clinical, biochemical and genetic analyses were performed in several members of one family, because the index case presented with elevated free TH, measurable TSH and no hyperthyroid manifestations, but with a pituitary lesion at MRI. High free TH levels and TSH concentrations in the normal range were found also in 4 relatives. The presence of euthyroidism in all patients together with peripheral parameters of TH action in the normal range led to the diagnosis of generalized RTH (GRTH). In the five affected members, the genetic analysis revealed a novel heterozygous missense mutation at codon 334 (M334T). A different mutation at codon 334 was previously described in association with selective pituitary resistance to thyroid hormone (PRTH). Therefore, we confirm that substitutions at Methionine 334 are critical for the structural integrity of TRβ LBD. The association of different phenotypes with substitutions affecting the same codon is another contribution confirming that RTH phenotype does not generally depend upon the site of the mutation in the LBD of TRβ1.
KW - ACE
KW - Glycoprotein α-subunit (α-GSU)
KW - ICTP
KW - Mutation
KW - Peripheral parameters
KW - Pituitary incidentaloma
KW - RTH
KW - SHBG
KW - Thyroid hormone resistance syndrome
KW - TRβ gene
UR - http://www.scopus.com/inward/record.url?scp=0036123390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036123390&partnerID=8YFLogxK
M3 - Article
C2 - 11929097
AN - SCOPUS:0036123390
VL - 25
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
SN - 0391-4097
IS - 2
ER -