Details Of Published TSH Receptor Mutation
Arg 450 His
c.1349G>AInactivating TSH Receptor Mutation
Type
loss
Manifestation
sporadic
Exon
10
Molecular Characteristics:
Sugisawa et al. compound heterozygous R109Q and R450H
Calebiro: 1 HET individual
2 unrelated individuals Kanda et al.
Yamaguchi et al. 2 homozygous and 2 compound heterozygous with C390F
Wang et al. 1 case SNAH
Calebiro: 1 HET individual
2 unrelated individuals Kanda et al.
Yamaguchi et al. 2 homozygous and 2 compound heterozygous with C390F
Wang et al. 1 case SNAH
Clinical Features:
default
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
9
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:
Calebiro et al.
J Clin Endocrinol Metab 97:156-160.
Frequent TSH Receptor Genetic Alterations with Variable Signaling Impairment in a Large Series of Children with Nonautoimmune Isolated Hyperthyrotropinemia.
2012
Reference 2:
Kanda et al.
Endocrine 30:383-388.
Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese.
2006
Reference 3:
Long W, Lu G, Zhou W, Yang Y, Zhang B, Zhou H, Jiang L, Yu B
Endocrine journal
Targeted next-generation sequencing of thirteen causative genes in Chinese patients with congenital hypothyroidism
2018
Reference 4:
Sugisawa et al.
Clin Pediatr Endocrinol
Identification of compound heterozygous TSHR mutations (R109Q and R450H) in a patient with nonclassic TSH resistance and functional characterization of the mutant receptors.
2018
Reference 5:
Yamaguchi et al.
JCEM
Targeted next-generation sequencing for congenital hypothyroidism with positive neonatal TSH screening
2020