Details Of Published TSH Receptor Mutation
Glu 575 Lys
c.1723G>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Nishihara 2014
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
2010:No symptoms of hyperthyroidism. Three years follow-up without tendency of thyroid growth.
Clinical Features:
2010:diagnosis: subclinical hyperthyroidism in all patients
I/1: 64yr (index patient), nodular goiter (40ml)
I/1: Anti-TPO antibodies and anti-TG antibodies positive. TSHR-Ab negative
2014: subclinical hyperthyroidism, II/3 61y III/1 39y III/3 30y II/3 Tg-Antibodies and TPO antibodies positive
*based on 1 activating familial germline mutation investigated by Nishihara et al. 2010 and 2014
I/1: 64yr (index patient), nodular goiter (40ml)
I/1: Anti-TPO antibodies and anti-TG antibodies positive. TSHR-Ab negative
2014: subclinical hyperthyroidism, II/3 61y III/1 39y III/3 30y II/3 Tg-Antibodies and TPO antibodies positive
*based on 1 activating familial germline mutation investigated by Nishihara et al. 2010 and 2014
Treatment:
none
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.0
2.42?±?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:
Nishihara et al.
Thyroid. 20:1307-14
Subclinical nonautoimmune hyperthyroidism in a family segregates with a thyrotropin receptor mutation with weakly increased constitutive activity.
2010
Reference 2:
Nishihara, Eijun, et al.
Thyroid
Prevalence of thyrotropin receptor germline mutations and clinical courses in 89 hyperthyroid patients with diffuse goiter and negative anti-thyrotropin receptor antibodies.
2014