Details Of Published TSH Receptor Mutation
Cys 636 Trp
c.1908C>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Pedigree 1 - Winkler et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default
Clinical Features:
diagonsis:
I/1: in adulthood
II/1: 5.5 yr
II/1: slightly irritable patient, tachycardia, Antibodies negative
*based on 1 activating familial germline mutation investigated by Winkler et al. 2010
I/1: in adulthood
II/1: 5.5 yr
II/1: slightly irritable patient, tachycardia, Antibodies negative
*based on 1 activating familial germline mutation investigated by Winkler et al. 2010
Treatment:
I/1: antithyroid medication
II/1: antithyroid medication at 11 5/12 yr
II/1: antithyroid medication at 11 5/12 yr
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.9
0.9
0.2
1.0
0.2
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:
Winkler et al.
J Clin Endocrinol Metab.95:3605-10
A new phenotype of nongoitrous and nonautoimmune hyperthyroidism caused by a heterozygous thyrotropin receptor mutation in transmembrane helix 6.
2010