Details Of Published TSH Receptor Mutation

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Phe 631 Ser

c.1892T>C

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
family
Exon
10
Pedigree 1 - Nwosu et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default 
Clinical Features:
diagnosis:
I/1: 42yr (index patient)
II/1: 19yr, goiter
II/2: 11yr, goiter
II/3: 10yr, goiter

I/1: proptosis
II/3: premature birth (30 weeks)

* based on 1 activating familial germline mutation investigated by Nwosu et al. 2006 
Treatment:
I/1: radio-iodine therapy (6mCi), L-T4
II/1, II/3: antithyroid drugs
II/2: antithyroid drugs discontinued because of side effects
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7.0
1.0
1.0
0.4
0.4
1
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:
Nwosu et al.
Thyroid. 16: 505-12
A novel activating mutation in transmembrane helix 6 of the thyrotropin receptor as cause of hereditary nonautoimmune hyperthyroidism.
2006
Abstract In Medline Available