Details Of Published TSH Receptor Mutation
Lys 58
DelExon2Inactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
2
Pedigree 1 - Cangul et al.
Legend:
Male
Female
Unknown
Deceased
+
Mutation
-
Wild-Type
Heterozygous
Heterozygous
Compound Heterozygous
Homozygous
Hypothyroid
Hypoplastic Gland + Hypothyroid
P
Index Patient
Molecular Characteristics:
DelExon2
Deletion of Exon 2
Deletion of Exon 2
Clinical Features:
II/1, II/2: homozygous
I/1,I/2: heterozygous
Turkish family, consanguineous parents (I/1*, I/2*)
II/1, II/2: severe thyroid aplasia
delayed neuromotor development, impaired cognitive development
I/1,I/2: heterozygous
Turkish family, consanguineous parents (I/1*, I/2*)
II/1, II/2: severe thyroid aplasia
delayed neuromotor development, impaired cognitive development
Treatment:
II/1 irregularly administered LT4 (20 days), carbamazepine (2.5 yo, reintroduced 13 yo), II/2 regularly administered LT4
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:
Cangul et al.
Clin Endocrinol (Oxf) 73:671-677.
Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism.
2010