Details Of Published TSH Receptor Mutation
Phe 631 Leu
c.1893C>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
multiple cDNA changes documented:
TTC>TTA,CTC,TTG
TTC>TTA,CTC,TTG
Clinical Features:
based on 20 hot nodules investigated by Parma et al. 1995 and 1997, Holzapfel et al. 1997, Fuhrer et al. 1997, Gozu et al. 2006, Trulzsch et al. 2001, Sancak et al. 2011, Nishihara et al. 2009 and Palos-Paz et al. 2008
and on 1 activating sporadic germline mutation investigated by Kopp et al. 1995
and on 1 activating sporadic germline mutation investigated by Kopp et al. 1995
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.0
1.0
n.d.
1.0
-
n.d.
20
45.9±9.4
1,11
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:
Kopp et al.
N Engl J Med. 332: 150-54
Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene
1995
Reference 2:
Parma et al.
Mol. Endocrinol. 9: 725-733
Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3',5'-monophosphate and inositol phosphate-Ca
1995
Reference 3:
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 4:
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 5:
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 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:
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 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:
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