Details Of Published TSH Receptor Mutation
Ser 505 Asn
c.1513G>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 4 hot nodules investigated by Trülzsch et al. 2001, Gozu et al. 2006 Stephenson et al. 2020, and Nishihara et al. 2009
and on 2 activating sporadic germline mutations investigated by Holzapfel et al. 1997 and Fuhrer et al. 1999
and on 1 activating familial germline mutation investigated by Vaidya et al. 2004
and on 2 activating sporadic germline mutations investigated by Holzapfel et al. 1997 and Fuhrer et al. 1999
and on 1 activating familial germline mutation investigated by Vaidya et al. 2004
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5-6.5
1.1
0.8-0.9
1-1.2
0.8
4
4.5+/-0.3
1,2,5,7
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: 3879-3884
Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene
1997
Reference 2:
Wonerow et al.
Clin. Endocrinol. 53: 461-468
Functional characterization of five constitutively activating thyrotrophin receptor mutations
2000
Reference 3:
Trülzsch et al.
J. Mol. Med. 78: 684-691
Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
2001
Reference 4:
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 5:
Jäschke et al.
Horm Metab Res. 43:500-4
Prolonged inappropriate TSH suppression during hypothyroidism after thyroid ablation in a patient with nonautoimmune familial hyperthyroidism.
2011
Reference 6:
Nishihara et al.
Endocr J. 56:791-8
Prevalence of TSH receptor and Gsalpha mutations in 45 autonomously functioning thyroid nodules in Japan.
2009
Reference 7:
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
Reference 8:
Stephenson et al.
Thyroid
Sensitive Sequencing Analysis Suggests Thyrotropin
Receptor and Guanine Nucleotide-Binding Protein G Subunit
Alpha as Sole Driver Mutations in Hot Thyroid Nodules
2020