Details Of Published TSH Receptor Mutation
Asp 633 Tyr
c1897G>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
carcinoma
Exon
10
Molecular Characteristics:
default
Clinical Features:
follicular carcinoma with clinical phenotype of "hot nodule"
*based on 15 hot nodules investigated by Porcellini et al. 1994, Parma et al. 1997, Russo et al. 1996, Nogueira et al. 1999, Gozu et al. 2005 and 2006, Trulzsch et al. 2001 and Palos-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
*based on 15 hot nodules investigated by Porcellini et al. 1994, Parma et al. 1997, Russo et al. 1996, Nogueira et al. 1999, Gozu et al. 2005 and 2006, Trulzsch et al. 2001 and Palos-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
-
n.d.
1
16.4±6.4
1,3
Legend:
cAMP (basal): basal in vitro cAMP production of mutant over wild-type TSHR
cAMP (TSH): maximal in vitro cAMP production of mutant over wild-type TSHR
IP (basal): basal in vitro IP production of mutant over wild-type TSHR
IP (TSH): maximal in vitro IP production of mutant over wild-type TSHR
TSH-binding: maximal TSH-binding compared to the wild-type TSHR
Cell surface expression: cell surface expression of mutant compared to WT-TSHR
LRA: linear regression analysis (LRA) of constitutive activity as a function of TSHR expression determined by 125I-bTSH binding or FACS analysis compared to the wild-type TSHR
Prevalence: Prevalence of (somatic and germline) activating mutations*
Ref: Reference for functional characterization
Child: Found in children.
Reference 1:
Kosugi et al.
FEBS Lett 356: 291-294
Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor.
1994
Reference 2:
Führer et al.
Endocr Relat Cancer. 10:591-600
Two somatic TSH receptor mutations in a patient with toxic metastasising follicular thyroid carcinoma and non-functional lung metastases.
2003
Reference 3:
Lüblinghoff et al.
J Endocrinol Invest 33:228-233
Lack of consistent association of thyrotropin receptor mutations in vitro activity with the clinical course of patients with sporadic non-autoimmune hyperthyroidism.
2010