Details Of Published TSH Receptor Mutation

Ile 167 Asn

c.500T>A

Inactivating TSH Receptor Mutation

Type
loss
Manifestation
family
Exon
6
Pedigree 1 - Sunthornthepvarakui et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
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
0
0
nd
nd
0
0
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:
Sunthornthepvarakui et al.
N. Engl. J. Med. 332: 155-157
Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene
1995
Reference 2:
Costagliola et al.
Thyroid 9: 995-1000
Structure-function relationships of two loss-of-function mutations of the thyrotropin receptor gene
1999