Details Of Published TSH Receptor Mutation
Asp 403 Asn
c.1207G>AInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Camilot et al.
Pedigree 2 - Nicoletti et al.
Pedigree 3 - Narumi 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 (Camilot et al.):
girl: mother: heterozygous
Family 1 - pedigree 1 (Nicoletti et al.):
prop and father heterozygous
Narumi et al.:
Patient 3: compound heterozygous Asp403Asn/Arg450His
girl: mother: heterozygous
Family 1 - pedigree 1 (Nicoletti et al.):
prop and father heterozygous
Narumi et al.:
Patient 3: compound heterozygous Asp403Asn/Arg450His
Clinical Features:
Family 1 - pedigree 1 (Camilot et al.):
subclinical hypothyroidism
isolated hyperthyrotrophinaemia
Family 1 - pedigree 1 (Nicoletti et al.):
hypoplastic thyroid
Narumi et al.:
diagnosed at 5yrs TSH elevated
subclinical hypothyroidism
isolated hyperthyrotrophinaemia
Family 1 - pedigree 1 (Nicoletti et al.):
hypoplastic thyroid
Narumi et al.:
diagnosed at 5yrs TSH elevated
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
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:
Camilot et al.
Clin Endocrinol (Oxf) 63:146-151.
Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes.
2005
Reference 2:
Narumi et al.
J Clin Endocrinol Metab 94:1317-1323.
TSHR mutations as a cause of congenital hypothyroidism in Japan: a population-based genetic epidemiology study.
2009
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