Details Of Published TSH Receptor Mutation
Ala 623 Ser
c.1867G>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 7 hot nodules investigated by Russo et al. 1996 and 1997 and Derwahl et al. 1996
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.5
n.d.
n.d.
n.d.
nd
n.d.
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:
Russo et al.
J. Clin. Endocrinol. Metab. 81: 1548-1551
Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas
1996
Reference 2:
Russo et al.
J. Clin. Endocrinol. Metab. 80: 1347-1351
Genetic alterations in thyroid hyperfunctioning adenomas
1995
Reference 3:
Derwahl et al.
J Clin Endocrinol Metab.81: 1898-904
Constitutive activation of the Gs alpha protein-adenylate cyclase pathway may not be sufficient to generate toxic thyroid adenomas.
1996