Details Of Published TSH Receptor Mutation

Leu 512 Met

c.1534C>A

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
sporadic
Exon
10
Molecular Characteristics:
No published data for in vitro characterization 
Clinical Features:
neonatal hyperthyroidism characterized by accelerated growth, enlarging head circumference, tremor and thyrotoxicosis in 6mo 
Treatment:
antithyroid drug, long term plan includes either near total thyroidectomy or radioactive iodine ablation
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
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:
Roberts et al.
Journal of Pediatric Endocrinology and Metabolism 
Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism.
2017