Details Of Published TSH Receptor Mutation
Leu 665 Phe
CTC -> TTCConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Jaeschke et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default
Clinical Features:
III/1 NAH, diagnosed during first pregnancy Iv/1-4 hyperthyroidism, TSH suppression in IV/3 at 8 years, IV/4 cognitive diasability, II/1 toxic multinodular goiter 36 years
Treatment:
III/1thiamazole, thyroid surgery. II/1: thyroid surgery. III/2: thyroid surgery for toxic nodular goiter. IV/1 and III/2 thiamazol therapy, IV/3 no therapy, IV/4 (4yo) thiamazol.
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
1.2
1
1.1
nd
1.02
1
2.3
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:
Jaeschke et al.
JCEM
A Newly Discovered TSHR Variant (L665F) Associated With Nonautoimmune Hyperthyroidism in an Austrian Family Induces Constitutive TSHR Activation by Steric Repulsion Between TM1 and TM7
2014