Details Of Published TSH Receptor Mutation

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Asn 406

del1 -> deletio

Inactivating TSH Receptor Mutation

Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Biebermann et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
deletion (18bp) / insertion (4bp) mutation with resulting frameshift starting codon 406, premature stop codon after amino acid position 419
creates a novel unique BsaAl restriction site 
Clinical Features:
pedigree 1 (Biebermann et al.):
I/1, II/2: Cys390Trp/wt
I/2: DelPhe406-Trp420/wt
II/1: Cys390Trp/DelPhe406-Trp420
compound heterozygous

II/1: hypothyroid at birth, reduced thyroid volume
I/2: hypothyroid, small thyroid volume (5 ml)
I/1, II/2: euthyroid 
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
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:
Biebermann et al.
J. Clin. Endocrinol. Metabol. 82: 3471-3480
Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism
1997
Abstract In Medline Available