Details Of Published TSH Receptor Mutation
Cys 41
-> 4bp dupInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
1
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:
41TGCAIns
4bp duplication: 41TGCAIns, frameshift mutation
premature stop at Codon 62 Q8fsX62
4bp duplication: 41TGCAIns, frameshift mutation
premature stop at Codon 62 Q8fsX62
Clinical Features:
II/1 13yr (propositus), euthyroid hyperthyrotropinaemia
II/1 (proband), II/2 (sister), I/1 (father) : heterozygous
II/2: TSH elevated, 9yr
I/1 (mother): wild type
II/1 (proband), II/2 (sister), I/1 (father) : heterozygous
II/2: TSH elevated, 9yr
I/1 (mother): wild type
Treatment:
II/1 : L-T4 for 1yr
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
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.
Clin Endocrinol (Oxf) 67:712-718.
Identification of TSH receptor mutations in three families with resistance to TSH.
2007