Details Of Published TSH Receptor Mutation
Arg 519 Cys
c.1555C>TInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Tsunekawa et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
Tsunekawa et al. (Family B):
proposita (B), twin sister*, brother):
R450H/R519C
coumpound heterozygous
father: R450H
mother: R519C
Lee et al.:
1 affected family
proposita (B), twin sister*, brother):
R450H/R519C
coumpound heterozygous
father: R450H
mother: R519C
Lee et al.:
1 affected family
Clinical Features:
Tsunekawa et al. (Family B):
elevated TSH, normal development
Lee et al. number of affected patients not given
elevated TSH, normal development
Lee et al. number of affected patients not given
Treatment:
L-T4
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
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:
Lee et al.
Clin Endocrinol (Oxf) 75:715-721.
Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism.
2011
Reference 2:
Tsunekawa et al.
Thyroid 16:471-479.
Identification and functional analysis of novel inactivating thyrotropin receptor mutations in patients with thyrotropin resistance.
2006