Details Of Published TSH Receptor Mutation
Val 597 Leu
c.1789G>CConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
sporadic
Exon
10
Pedigree 1
-image missing-
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default
Clinical Features:
onset and diagnosis:
II/1: 9 months, diffuse goiter, advanced bone age
* based on 1 hot nodule investigated by Palo-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Esapa et al. 1999
II/1: 9 months, diffuse goiter, advanced bone age
* based on 1 hot nodule investigated by Palo-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Esapa et al. 1999
Treatment:
no effect of antithyroid drugs
total TE at 14 months
total TE at 14 months
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-6.8
0.5
n.d.
n.d.
-
0.1-0.2
1
125.2±10.5
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:
Esapa et al.
Thyroid 9: 1005-10
A novel thyrotropin receptor mutation in an infant with severe thyrotoxicosis
1999
Reference 2:
Claeysen et al.
FEBS Lett 517: 195-200
A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist.
2002
Reference 3:
Mueller et al.
Thyroid. 19(7):765-73
Cases of borderline in vitro constitutive thyrotropin receptor activity: how to decide whether a thyrotropin receptor mutation is constitutively active or not?
2009