Details Of Published TSH Receptor Mutation

Asp 633 His

c1897G>C

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
carcinoma
Exon
10
Molecular Characteristics:
default 
Clinical Features:
thyroid insular cell carcinoma with clinical phenotype of "hot nodule"

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)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.2
0.7
2.2
1.0
nd
0.8
1
2
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