Details Of Published TSH Receptor Mutation
Arg 310 Cys
c.928C>TInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
10
Pedigree 1 - Russo et al.
-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 (Russo et al.):
Family 2 - pedigree 2 (Nicoletti et al.):
prop and mother heterozygous
Family 2 - pedigree 2 (Nicoletti et al.):
prop and mother heterozygous
Clinical Features:
Family 1 - pedigree 1 (Russo et al.):
euthyroid hyperthyrotropinaemia, normal thyroid gland, normal thyroid scan, 2 siblings
Family 2 - pedigree 2 (Nicoletti et al.):
propositus: attention deficit
mother: autoimmune thyroiditis and hypercholesterolaemia
euthyroid hyperthyrotropinaemia, normal thyroid gland, normal thyroid scan, 2 siblings
Family 2 - pedigree 2 (Nicoletti et al.):
propositus: attention deficit
mother: autoimmune thyroiditis and hypercholesterolaemia
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
+
0
nd
nd
(0)
nd
2
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:
Russo et al.
J. Clin. Endocrinol. Metab. 85: 4238-4242
A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH
2000
Reference 2:
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