Details Of Published TSH Receptor Mutation

Back To All Mutations

Thr 477 Ile

c.1431C>T

Inactivating TSH Receptor Mutation

Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Tonacchera et al
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
II/1-2: Thr477Ile
II/5: Thr477Ile
III/1: Thr477Ile/Thre477Ile homozygous
III/3-4: Thr477Ile 
Clinical Features:
diagnosis:
1 month, congenital hypothyroidism, hypoplastic gland on ultrasound, negative 131-I scan, undetectable serum Tg levels, mental retardation 
Treatment:
L-thyroxine
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
nd
-
(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:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 85: 1001-1008
Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene
2000
Abstract In Medline Available