Details Of Published TSH Receptor Mutation
Cys 672 Thr
c.2015G>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Pedigree 1 - Duprez et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
Pedigree 1: "Reims Family"
Clinical Features:
manifestation:
III/25: 19yr
IV/1: 18 months
IV/2, IV/3: 10 years
*based on 1 activating familial germline mutation investigated by Duprez et al. 1994
III/25: 19yr
IV/1: 18 months
IV/2, IV/3: 10 years
*based on 1 activating familial germline mutation investigated by Duprez et al. 1994
Treatment:
II/6: thyroid surgery
III/1: radio-iodine therapy
III/25: thyroid surgery
IV/1: carbimazole
III/1: radio-iodine therapy
III/25: thyroid surgery
IV/1: carbimazole
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-3.3
0.5-0.7
n.d.
n.d.
-
0.4
1
4.2±0.5
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:
Duprez et al.
Nature Genetics 7: 396-401
Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism
1994
Reference 2:
Russo et al.
Thyroid 9: 13-17
A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis
1999
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