Details Of Published TSH Receptor Mutation

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Ala 485 Val

c.1454T>C

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
family
Exon
10
Pedigree 1 - Akcurin et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default 
Clinical Features:
diagnosis:
II/1: 3.5yr (index patient), goiter
II/2: 12 days, goiter
I/1: 36yr, goiter

* based on 1 activating familial germline mutation investigated by Akcurin et al. 2008 
Treatment:
II/1: euthyroid but progressive thyroid enlargement with antithyroid medication
II/2: antithyroid drugs
I/1: antithyroid drugs ineffective, total TE at 36yr
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.7
n.d.
1.0
0.05
0.03
1
1,2
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:
Akcurin et al.
Eur J Pediatr. 167: 1231-7
A family with a novel TSH receptor activating germline mutation (p.Ala485Val).
2008
Abstract In Medline Available
Reference 2:
Sancak et al.
Horm Metab Res. 43:562-8
High Prevalence of TSHR/Gsalpha Mutation-negative Clonal Hot Thyroid Nodules (HNs) in a Turkish Cohort
2011
Abstract In Medline Available