Details Of Published TSH Receptor Mutation
Leu 512 Arg
c.1535T>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
carcinoma
Exon
10
Molecular Characteristics:
default
Clinical Features:
papillary carcinoma with clinical phenotype "hot nodule"
based on 7 hot nodules investigated by Kosugi et al. 2000, Trülzsch et al. 2001, Gozu et al. 2006, Paloz-Paz et al. 2008 and Vanvooren et al. 2002
and on 1 hot thyroid carcinoma investigated by Gozu et al. 2004
based on 7 hot nodules investigated by Kosugi et al. 2000, Trülzsch et al. 2001, Gozu et al. 2006, Paloz-Paz et al. 2008 and Vanvooren et al. 2002
and on 1 hot thyroid carcinoma investigated by Gozu et al. 2004
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3
0.5
1.0
0.1
0.6
1
1
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.
Eur. J. Endocrinol. 143: 471-477
A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient
2000
Reference 2:
Gözu et al.
Thyroid. 14:975-80
Does a Leu 512 Arg thyrotropin receptor mutation cause an autonomously functioning papillary carcinoma?
2004