Details Of Published TSH Receptor Mutation
Asn 650 Tyr
c.1948A>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
family
Exon
10
Pedigree 1 - Tonacchera et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
No Mutation
Hyperthyroidism
(Heterozygous)
(Heterozygous)
Goiter
Relapse
P
Index Patient
Molecular Characteristics:
Pedigree 1: "Belfort Family"
Clinical Features:
manifestation:
III/1: 14 yr
III/2: 23 yr
III/1, III/2:
diffuse goiter
I/1, II/1, II/2:
multinodular goiter
*based on 1 activating familial germline mutation investigated by Tonacchera et al. 1996
III/1: 14 yr
III/2: 23 yr
III/1, III/2:
diffuse goiter
I/1, II/1, II/2:
multinodular goiter
*based on 1 activating familial germline mutation investigated by Tonacchera et al. 1996
Treatment:
I/1, II/1, II/2: goiter and hyperthyroidism recurred after subtotal thyroidectomy
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.6
1.0
1.0
n.d.
~
n.d.
1
1
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:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 81: 547-554
Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia
1996