Details Of Published TSH Receptor Mutation

Phe 631 Leu

c.1891T>C

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
sporadic
Exon
10
Pedigree 1 (Kopp et al.)
-image missing-
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
default 
Clinical Features:
onset and diagnosis:
III/2: neonatal, diffuse goiter

mental retardation, hyperactivity

II/3: hyperthyroid

* based on 23 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 
Treatment:
III/2: antithyroid drugs, relapse after pause, progressive multinodular goiter,
subtotal TE at 8.7yr, relapse, radioiodine at 9.2yr, euthyroid
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.0
1.0
n.d.
1.0
-
n.d.
1
45.9┬▒9.4
1,3
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:
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 3:
L├╝blinghoff 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