Details Of Published TSH Receptor Mutation

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Ile 167 Asn

c.500T>A

Inactivating TSH Receptor Mutation

Type

loss

Manifestation

family

Exon

Pedigree 1 - Sunthornthepvarakui et al.

Legend:

Male

Female

Unknown

Deceased

Mutation

Wild-Type

Heterozygous

Compound Heterozygous

Homozygous

Hypothyroid

Hypoplastic Gland + Hypothyroid

Index Patient

Molecular Characteristics:

pedigree 1:
I/1: Ile167Asn
I/2: Pro162Ala/Pro52Thr
II/1-3: Pro162Ala/Ile167Asn
compound heterozygous
polymorphism Pro52Thr in I/2

Clinical Features:

pedigree 1:
diagnosis:
II/1: 4yr
II/2: neonatal
II/3: neonatal, euthyroid hyperthyrotropinaemia, normal scintiscan
I/1 and I/2: borderline TSH levels

Treatment:

default

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:

Sunthornthepvarakui et al.

N. Engl. J. Med. 332: 155-157

Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene

1995

Abstract In Medline Available

Reference 2:

Costagliola et al.

Thyroid 9: 995-1000

Structure-function relationships of two loss-of-function mutations of the thyrotropin receptor gene

1999

Abstract In Medline Available