Details Of Published TSH Receptor Mutation
Ala 428 Val
c.1283C>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Pedigree 1 (Börgel et al.)
-image missing-
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default
Clinical Features:
onset and diagnosis:
III/1: neonatal
Goiter at 4.6yr
II/1: diagnosis during adolescence, multi-nodular goiter
I/1: euthyroid nodular goiter
*based on 2 hot nodules investigated by Gozu et al. 2006
and 2 activating familial germline mutation investigated by Börgel et al. 2005 and Guemas 2003
III/1: neonatal
Goiter at 4.6yr
II/1: diagnosis during adolescence, multi-nodular goiter
I/1: euthyroid nodular goiter
*based on 2 hot nodules investigated by Gozu et al. 2006
and 2 activating familial germline mutation investigated by Börgel et al. 2005 and Guemas 2003
Treatment:
III/1: longterm carbimazole treatment (5.9yr)
II/1: antithyroid drugs, subtotal TE at 16yr
II/1: antithyroid drugs, subtotal TE at 16yr
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.4
0.9
n.d.
n.d.
0.25
2
88.2+/-2.1
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:
Börgel et al.
Horm Res. 64:203-8
Long-term carbimazole treatment of neonatal nonautoimmune hyperthyroidism due to a new activating TSH receptor gene mutation (Ala428Val).
2005
Reference 3:
Guemas et al.
Hormone Research (supplement)
Hyperthyroidism due to an activation mutation of the thyrotropin receptor
2003