Details Of Published TSH Receptor Mutation
Asp 633 Tyr
c1897G>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
sporadic
Exon
10
Pedigree 1 (Bircan 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:
II/1: 1.5 months, premature birth (33 weeks)
diagnosis:
II/1: 6 months, diffuse goiter, advanced bone age, proptosis, periorbital edema, craniosynostosis
*based on 12 hot nodules investigated by Porcellini et al. 1994, Parma et al. 1997, Russo et al. 1996, Nogueira et al. 1999, Gozu et al. 2005 and 2006, Trulzsch et al. 2001 and Palos-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
II/1: 1.5 months, premature birth (33 weeks)
diagnosis:
II/1: 6 months, diffuse goiter, advanced bone age, proptosis, periorbital edema, craniosynostosis
*based on 12 hot nodules investigated by Porcellini et al. 1994, Parma et al. 1997, Russo et al. 1996, Nogueira et al. 1999, Gozu et al. 2005 and 2006, Trulzsch et al. 2001 and Palos-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
Treatment:
II/1: antithyroid drugs ineffective, subtotal TE at 10yr, relapse of hyperthyroidism at 11, 13, 20, 21yr
subtotal TE of left lobe at 14yrs, total resection of left lobe and near-totalresection of right lobe at 20yr
subtotal TE of left lobe at 14yrs, total resection of left lobe and near-totalresection of right lobe at 20yr
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
ND
ND
1
16.4±6.4
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:
Kosugi et al.
FEBS Lett 356: 291-294
Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor.
1994
Reference 2:
Bircan et al.
Exp Clin Endocrinol Diabetes. 116:341-6
Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism.
2008
Reference 3:
Lüblinghoff et al.
J Endocrinol Invest 33:228-233
Lack of consistent association of thyrotropin receptor mutations in vitro activity with the clinical course of patients with sporadic non-autoimmune hyperthyroidism.
2010