Details Of Published TSH Receptor Mutation
Asp 619 Gly
c.1856A>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 19 hot nodules investigated by Parma et al. 1993, Fuhrer et al. 1997, Tonacchera et al. 1998 and 1999, Noguiera et al. 1999, Trülzsch et al. 2001, Van Sande et al. 1995, Tassi et al. 1999, Gozu et al. 2006, Paloz-Paz et al. 2008 and Stephenson et al. 2020
Treatment:
Tonacchera et al. 1999: preoperative treatment with methimazole and iodide, thyroid lobectomy
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-1.8
0.9-1.0
0.9
0.8-0.9
-
0.6
19
1,11,12
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.
Nature 365: 649-651
Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas
1993
Reference 2:
Fuhrer et al.
J. Clin. Endocrinol. Metab. 82: 3885-3891
Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules
1997
Reference 3:
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 4:
Nogueira et al.
Thyroid 9: 1063-1068
Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil
1999
Reference 5:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 84: 4155-4158
Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms
1999
Reference 6:
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 7:
Van Sande et al.
J. Clin. Endocrinol. Metab. 80: 2577-2585
Somatic and germline mutations of the TSH receptor gene in thyroid diseases
1995
Reference 8:
Tassi et al.
Thyroid 9: 353-357
Screening of thyrotropin receptor mutations by fine-needle aspiration biopsy in autonomous functioning thyroid nodules in multinodular goiters
1999
Reference 9:
Claeysen et al.
FEBS Lett 517: 195-200
A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist.
2002
Reference 10:
Nishihara et al.
Endocr J. 54: 927-34
A novel thyrotropin receptor germline mutation (Asp617Tyr) causing hereditary hyperthyroidism.
2007
Reference 11:
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 12:
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 13:
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