Details Of Published TSH Receptor Mutation
Ile 568 Phe
c.1702A>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on four cases of hot nodules: toxic follicular adenoma by Agretti et al., ATN by Schwab et al., and adenomatous goitre by Schwab et al. and Nanba et al. 2012
Treatment:
thyroidectomy
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.4
1.1
nd
nd
1
nd
3
nd
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:
Schwab, Karl Otfried, et al.
The Journal of Pediatrics
Autonomous thyroid adenoma: only an adulthood disease?
2009
Reference 2:
Nanba, Kazutaka, et al.
Endocrine journal
Two rare TSH receptor amino acid substitutions in toxic thyroid adenomas
2012
Reference 3:
Agretti et al.
Clinical endocrinology
Prevalence of activating thyrotropin receptor and gsa gene mutations in paediatric thyroid toxic adenomas: a multicentric italian study
2013