Details Of Published TSH Receptor Mutation
Gly 245 Ser
c.733G>AInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
9
Pedigree 1 - Yuan et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
Family 1 - pedigree 1 (Yuan et al.):
propositus: Gly245Ser/wt
father: Gly245Ser/wt
mother: wt/wt
Lee et al.:
1 heterozygous individual
propositus: Gly245Ser/wt
father: Gly245Ser/wt
mother: wt/wt
Lee et al.:
1 heterozygous individual
Clinical Features:
Family 1 - pedigree 1 (Yuan et al.):
non-consanguineous Chinese parents
prop: diagnosis neonatal, normal thyroid ultrasound and Tc99m uptake
Ab negative, normal development
parents euthyroid
non-consanguineous Chinese parents
prop: diagnosis neonatal, normal thyroid ultrasound and Tc99m uptake
Ab negative, normal development
parents euthyroid
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
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:
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:
Yuan et al.
Endocr J 55:415-423.
Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism.
2008