Details Of Published TSH Receptor Mutation

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Ala 593 Asn

c.1778C>A; c.1777G>A

Constitutively Activating TSH Receptor Mutation

Type

gain

Manifestation

somatic

Exon

Molecular Characteristics:

default

Clinical Features:

based on 1 hot nodule investigated by Georgopoulos et al. 2003

Treatment:

default

Functional Characteristics:

cAMP
(basal)

cAMP
(TSH)

IP
(basal)

IP
(TSH)

TSH-Binding

Cell Surface Expression

Prevalence

LRA

Ref

4.4

1.3

n.d.

0.4

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:

Georgopoulos et al.

Eur J Endocrinol. 149: 287-92

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway.

2003

Abstract In Medline Available

Reference 2:

Sykiotis et al.

Biochem Biophys Res Commun 301:1051-1056

Functional significance of the thyrotropin receptor germline polymorphism D727E.

2003

Abstract In Medline Available