Details Of Published TSH Receptor Mutation
Leu 252 Pro
c.755T>CInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
9
Pedigree 1 - Tonacchera et al.
Pedigree 2 - Camilot 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 (Tonacchera et al.):
II/1 prop. heterozygous
I/2: mother: heterozygous
Family 2 - pedigree 2 (Camilot et al):
father, son: heterozygous
II/1 prop. heterozygous
I/2: mother: heterozygous
Family 2 - pedigree 2 (Camilot et al):
father, son: heterozygous
Clinical Features:
Family 1 - pedigree 1 (Tonacchera et al.):
II/1: 34 yr woman, hyperthyrotropinemia, no goiter
I/2: TSH elevated
I/1 and II/2 normal thyroid hormones
Family 2 - pedigree 2 (Camilot et al.):
son: subclinical hypothyroidism
II/1: 34 yr woman, hyperthyrotropinemia, no goiter
I/2: TSH elevated
I/1 and II/2 normal thyroid hormones
Family 2 - pedigree 2 (Camilot et al.):
son: subclinical hypothyroidism
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
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:
Camilot et al.
Clin Endocrinol (Oxf) 63:146-151.
Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes.
2005
Reference 2:
Tonacchera et al.
J Clin Endocrinol Metab 89:5787-5793.
Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism.
2004