Details Of Published TSH Receptor Mutation

Lys 183 Arg

c.548A>G

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
family
Exon
7
Pedigree 1 - Sunthornthepvarakui et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
promiscuous stimulation of
mutant K183R TSHR by hCG
(gestational thyrotoxicosis)

K183R nullifies AluI
restriction site

NOTE:
no constitutive activity 
Clinical Features:
manifestation:
II/1:
at 10 weeks 1. pregnancy and at 7 weeks 2. pregnancy (index patient)
I/2:
1. trimester of pregnancy 2 miscarriages 
Treatment:
antithyroid drugs
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
~
~
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:
Rodien et al.
N. Engl. J. Med. Vol 339: 1823-1826
Familial Gestational Hyperthroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to human Chorionic Gonadotropin
1998