Details Of Published TSH Receptor Mutation
Met 453 Arg
c.1358T>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Molecular Characteristics:
heterozygous M435R
Clinical Features:
I/1: 24 goiter NAH, uticaria developed 1 month after first treatment II/1: goiter at 9yo II/2NAH: no goiter at 1mo, tachycardia. Goiter at 2.5y.
Treatment:
I/1: thiamazole for 1 month, then propylthiouracil II/1: propylthiouracil II/2:thiamazole
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8.53 +/- 1
0.479+/-0.
1
0
nd
0.806+/-0.
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:
Nakamura et al.
Pediatric research
A Japanese family with nonautoimmune hyperthyroidism caused by a novel heterozygous thyrotropin receptor gene mutation
2014