Details Of Published TSH Receptor Mutation
Asn 406 Ser
c.1217A>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Molecular Characteristics:
no published data for in vitro activation
Clinical Features:
Fukata: child symptomatic, father asymptomatic
Okazaki: mother and daughter with FNAH during pregnancy
Okazaki: mother and daughter with FNAH during pregnancy
Treatment:
Fukata: RI therapy
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
224, 225
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:
Fukata et al
Clinical Endocrinology
A Japanese family with familial nonautoimmune
hyperthyroidism with a novel mutation (Asn406Ser)
in extracellular domain of thyrotrophin receptor
2012
Reference 2:
Okazaki et al. 2020
AACE Case Reports
A CASE OF FAMILIAL NONAUTOIMMUNE
HYPERTHYROIDISM DURING PREGNANCY
2020