Details Of Published TSH Receptor Mutation

Val 689 Gly

c.2066T>G

Inactivating TSH Receptor Mutation

Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Yuan et al.
Fu et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
propositus compound heterozygous
Val689Gly/Pro52Thr
mother: Pro52Thr/wt
father: Val689Gly/wt
Pro52Thr (polymorphism)
 
Clinical Features:
non-consanguineous Chinese parents
propositus neonatal diagnosis,TSH elevated
antibodies negative, normal thyroid size
parents: euthyroid
normal development
 
Treatment:
L-T4
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
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:
Yuan et al.
Endocr J 55:415-423.
Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism.
2008
Reference 2:
Fu, Chunyun et al.
Clinica Chimica Acta
Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients
2016