Details Of Published TSH Receptor Mutation

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Lys 183 Arg

c.548A>G

Constitutively Activating TSH Receptor Mutation

Type

gain

Manifestation

family

Exon

Pedigree 1 - Sunthornthepvarakui et al.

Legend:

Male

Female

Unknown

Deceased

Mutation

No Mutation

Hyperthyroidism
(Heterozygous)

Goiter

Relapse

Index Patient

Molecular Characteristics:

promiscuous stimulation of
mutant K183R TSHR by hCG
(gestational thyrotoxicosis)

K183R nullifies AluI
restriction site

NOTE:
no constitutive activity

Clinical Features:

manifestation:
II/1:
at 10 weeks 1. pregnancy and at 7 weeks 2. pregnancy (index patient)
I/2:
1. trimester of pregnancy 2 miscarriages

Treatment:

antithyroid drugs

Functional Characteristics:

cAMP
(basal)

cAMP
(TSH)

IP
(basal)

IP
(TSH)

TSH-Binding

Cell Surface Expression

Prevalence

LRA

Ref

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:

Rodien et al.

N. Engl. J. Med. Vol 339: 1823-1826

Familial Gestational Hyperthroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to human Chorionic Gonadotropin

1998

Abstract In Medline Available