Details Of Published TSH Receptor Mutation
Ile 486 Asn
c.1457T>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
sporadic
Exon
10
Pedigree 1 (Biebermann et al.)
-image missing-
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
sporadic occurence in 1 patient
Clinical Features:
onset: 1month, tachycardia, normal thyroid volume, low birth weight
* based on 1 hot nodule investigated by Gozu et al. 2006
and on 1 activating sporadic germline mutation investigated by Biebermann et al. 2011
* based on 1 hot nodule investigated by Gozu et al. 2006
and on 1 activating sporadic germline mutation investigated by Biebermann et al. 2011
Treatment:
antithyroid drugs at 2 months
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7.1
0.8
n.d.
n.d.
0.6
1
6.7+/-1.4
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:
Gozu et al.
Eur J Endocrinol. 155: 535-45
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
2006
Reference 2:
Biebermann et al.
Thyroid Res. 3 Suppl 1:8
Molecular description of non-autoimmune hyperthyroidism at a neonate caused by a new thyrotropin receptor germline mutation.
2011