Details Of Published TSH Receptor Mutation
Ile 630 Leu
c.1888A>CConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
sporadic
Exon
10
Pedigree 1 (Bertalan 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:
II/1: onset and diagnosis:
10mo, exsiccosis, unconsciousness,
fever, tachycardia, ICU treatment
Arnold-Chiari malformation 1,
staring eyes, progressive multi-nodular goiter
based on 11 hot nodules investigated by Parma et al. 1997, Holzapfel et al. 1997, Tonacchera et al. 1998, Gozu et al. 2005 and 2006, Palos-Paz et al. 2008 and Nishihara et al., 2009
and on 1 activating sporadic germline mutation investigated by Bertalan et al. 2010
10mo, exsiccosis, unconsciousness,
fever, tachycardia, ICU treatment
Arnold-Chiari malformation 1,
staring eyes, progressive multi-nodular goiter
based on 11 hot nodules investigated by Parma et al. 1997, Holzapfel et al. 1997, Tonacchera et al. 1998, Gozu et al. 2005 and 2006, Palos-Paz et al. 2008 and Nishihara et al., 2009
and on 1 activating sporadic germline mutation investigated by Bertalan et al. 2010
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.5-6.4
0.8-1.1
0.9
0.3
ND
0.4
1
ND
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:
Holzapfel et al.
J. Clin. Endocrinol. Metab. 82: 4229-4233
Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters
1997
Reference 2:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 83: 492-498
Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma
1998
Reference 3:
Wonerow et al.
Clin. Endocrinol. 53: 461-468
Functional characterization of five constitutively activating thyrotrophin receptor mutations
2000
Reference 4:
Bertalan et al.
Thyroid. 20:327-32
Hyperthyroidism caused by a germline activating mutation of the thyrotropin receptor gene: difficulties in diagnosis and therapy.
2010