Details Of Published TSH Receptor Mutation
Gln 90 Pro
c.269A>C; c.270G>TInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
3
Pedigree 1 - Sriphrapradang et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
One mutant allele, 4 base substitutions, producing 3 mutations L89L, Q90P, P246S
Coexistence of TPO mutations: G493S, R450X
found in three nuclear families
III/6: homozygous
Coexistence of TPO mutations: G493S, R450X
found in three nuclear families
III/6: homozygous
Clinical Features:
III-6 (Index case of family 2): male, with
congenital hypothyroidism at 3 weeks, euthyroid hyperthyrotropinaemia, no symptoms or signs of congenital hypothyroidsim.
At 2 yrs, L-T4 withdrawal and tests
revealed primary hypothyroidism
Eutopic thyroid gland on Tc 99m scan
congenital hypothyroidism at 3 weeks, euthyroid hyperthyrotropinaemia, no symptoms or signs of congenital hypothyroidsim.
At 2 yrs, L-T4 withdrawal and tests
revealed primary hypothyroidism
Eutopic thyroid gland on Tc 99m scan
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
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:
Sriphrapradang et al.
J Clin Endocrinol Metab 96:E1001-E1006.
The coexistence of a novel inactivating mutant thyrotropin receptor allele with two thyroid peroxidase mutations: a genotype-phenotype correlation.
2011