Details Of Published TSH Receptor Mutation

308

intron5/exon6 junction

Inactivating TSH Receptor Mutation

Type
loss
Manifestation
family
Exon
9
Pedigree 1
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
AG -> splice variant
mutation on intron5/exon6 junction, changing the canonical AG splicing acceptor site into AA 
Clinical Features:
II/2, II/5, II/6: homozygous splice variant
parents and other siblings heterozygous
splice variant
consanguineous North African parents

proposita: II/2, II/5, II/6
diagnosis:
neonatal, congenital hypothyroidism, persistent jaundice, myxedematous facies, umbilical hernia, enlarged fontanels, macroglossia, tachycardia, hypoplastic ectopic thyroid gland on ultrasound, negative 99mTc or 123-I scan

II/2: moderate pyschomotor delay, congenital ptosis 
Treatment:
L-T4
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(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:
Bretones et al.
Thyroid 11: 977-180
A familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene
2001