Details Of Published TSH Receptor Mutation
Asp 633 His
c1897G>CConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 13 hot nodules investigated by Parma et al. 1997, Russo et al. 1996, Gozu et al. 2005 and 2006, Trulzsch et al. 2001, Sancak et al. 2011, Palos-Paz et al. 2008, Nishihara et al. 2009, Eszlinger et al. 2014, Schwab et al.2009, Grob et al. 2014 and on 1 hot thyroid carcinoma investigated by Russo et al. 1997,
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.2
0.7
2.2
1.0
nd
0.8
13
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:
Parma et al.
J. Clin. Endocrinol. Metab. 82: 2695-2701
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas
1997
Reference 2:
Russo et al.
J. Clin. Endocrinol. Metab. 80: 1347-1351
Genetic alterations in thyroid hyperfunctioning adenomas
1995
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:
Neumann et al.
Mol. Endocrinol. 15: 1294-1305
A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation.
2001
Reference 5:
Russo et al.
J. Clin. Endocrinol. Metab. 82: 3906-3908
Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma
1997
Reference 6:
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 7:
Palos-Paz et al.
Eur J Endocrinol. 159: 623-31
Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.
2008
Reference 8:
Gozu et al.
Endocr J. 52: 577-85
Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population.
2005
Reference 9:
Sancak et al.
Horm Metab Res. 43:562-8
High Prevalence of TSHR/Gsalpha Mutation-negative Clonal Hot Thyroid Nodules (HNs) in a Turkish Cohort
2011
Reference 10:
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 11:
Schwab, Karl Otfried, et al.
The Journal of Pediatrics
Autonomous thyroid adenoma: only an adulthood disease?
2009
Reference 12:
Eszlinger, Markus, et al.
Molecular and cellular endocrinology
Somatic mutations in 33 benign and malignant hot thyroid nodules in children and adolescents
2014
Reference 13:
Grob et al.
Hormone research in pediatrics
Autonomous adenomas caused by somatic mutations of the thyroid-stimulating hormone receptor in children
2014