Details Of Published TSH Receptor Mutation
Ala 623 Phe
c.1867G>T; c.1868C>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 1 hot nodule investigated by Paloz-Paz et al. 2008 and characterized by Castro et al. 2009.
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.3-0.4
1.0
n.d.
n.d.
0.5
1
1,2
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:
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 2:
Castro et al.
Thyroid 19:645-649
Identification and functional characterization of two novel activating thyrotropin receptor mutants in toxic thyroid follicular adenomas.
2009