Details Of Published TSH Receptor Mutation

Leu 512 Arg

c.1535T>G

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default 
Clinical Features:
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)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3
0.5
1.0
0.1
-
0.6
7
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:
Trülzsch et al.
J. Mol. Med. 78: 684-691
Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
2001
Reference 3:
Gozu et al.
Eur J Endocrinol. 155: 535-45
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
2006
Reference 4:
Palos-Paz et al.
Eur J Endocrinol. 159: 623-31
Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.
2008
Reference 5:
Vanvooren et al.
Eur J Endocrinol. 147: 287-91
Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.
2002