Details Of Published TSH Receptor Mutation
Phe 525 Leu
c.1575C>AInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1 - De Roux et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
I/1: Cys41Ser
I/2: Phe525Leu
II/1: Cys41Ser/Phe525Leu compound heterozygous (Cys41)
I/2: Phe525Leu
II/1: Cys41Ser/Phe525Leu compound heterozygous (Cys41)
Clinical Features:
diagnosis:
II/1 neonatal, euthyroid hyperthyrotropinaemia, normal gland on 123-I scan, normal Tg levels
II/1 neonatal, euthyroid hyperthyrotropinaemia, normal gland on 123-I scan, normal Tg levels
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
nd
nd
~
-
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:
De Roux et al.
J. Clin. Endocrinol. Metabol. 81: 4229-4235
Four families with loss of function mutations of the thyrotropin receptor
1996