Details Of Published TSH Receptor Mutation
Gln 324 Stop
c.970C>TInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
I/1: Gln324Stop
I/2: Asp410Asn
II/1-2: Gln324Stop/Asp410Asn compound heterozygous
I/2: Asp410Asn
II/1-2: Gln324Stop/Asp410Asn compound heterozygous
Clinical Features:
diagnosis:
II/1-2: neonatal, II/1-3, III/1, III/3-4euthyroid hyperthyrotropinaemia, slightly enlarged gland on 123-I scan, normal Tg level
II/1-2: neonatal, II/1-3, III/1, III/3-4euthyroid hyperthyrotropinaemia, slightly enlarged gland on 123-I scan, normal Tg level
Treatment:
L-thyroxine
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
nd
nd
nd
nd
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