Details Of Published TSH Receptor Mutation
Cys 390 Trp
c.1170T>GInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1 - De Roux et al.
Pedigree 2 - Nicoletti et al.
Pedigree 3 - Biebermann et al.
test
-image missing-
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 (de Roux et al.):
I/1: Cys390Trp
I/2: Trp546Stop
II/1: Cys390Trp/Trp546Stop
compound heterozygous
Family 2 - pedigree 2 (Nicoletti et al.):
propositus and mother
heterozygous
Family 3 - pedigree 3 (Biebermann et al.):
I/1, I/2, II/2: Cys390Trp/wt
II/1:Cys390Trp/DelPhe406-Trp420
compound heterozygous
I/1: Cys390Trp
I/2: Trp546Stop
II/1: Cys390Trp/Trp546Stop
compound heterozygous
Family 2 - pedigree 2 (Nicoletti et al.):
propositus and mother
heterozygous
Family 3 - pedigree 3 (Biebermann et al.):
I/1, I/2, II/2: Cys390Trp/wt
II/1:Cys390Trp/DelPhe406-Trp420
compound heterozygous
Clinical Features:
Family 1 - pedigree 1 (de Roux et al.):
small goiter
Family 2 - pedigree 2 (Nicoletti et al.):
propositus: obesity
Family 3 - pedigree 3 (Biebermann et al.):
II/1: hypothyroid at birth, reduced thyroid volume
I/2: hypothyroid, small thyroid volume (5 ml)
I/1, II/2: euthyroid
small goiter
Family 2 - pedigree 2 (Nicoletti et al.):
propositus: obesity
Family 3 - pedigree 3 (Biebermann et al.):
II/1: hypothyroid at birth, reduced thyroid volume
I/2: hypothyroid, small thyroid volume (5 ml)
I/1, II/2: euthyroid
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
+
-
3
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:
Biebermann et al.
J. Clin. Endocrinol. Metabol. 82: 3471-3480
Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism
1997
Reference 2:
De Roux et al.
J. Clin. Endocrinol. Metabol. 81: 4229-4235
Four families with loss of function mutations of the thyrotropin receptor
1996
Reference 3:
Nicoletti et al.
J Clin Endocrinol Metab 94:4187-4194.
Thyrotropin-stimulating hormone receptor gene analysis in pediatric patients with non-autoimmune subclinical hypothyroidism.
2009