Details Of Published TSH Receptor Mutation
Cys 41 Ser
c.122G>CInactivating TSH Receptor Mutation
Type
loss
Manifestation
family
Exon
1
de Roux et al.
Alberti et al.
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 (de Roux et al.):
I/1: Cys41Ser
I/2: Phe525Leu
II/1: Cys41Ser/Phe525Leu compound heterozygous
Family 2 - Pedigree 2 (Alberti et al.):
I/1: Cys41Ser
II/1: Cys41Ser heterozygous
Family 3 (Camilot et al):
8 heterozygous patients
Calebiro et al:
four unrelated heterozygous patients
Vigone et al. 2 families C41S
I/1: Cys41Ser
I/2: Phe525Leu
II/1: Cys41Ser/Phe525Leu compound heterozygous
Family 2 - Pedigree 2 (Alberti et al.):
I/1: Cys41Ser
II/1: Cys41Ser heterozygous
Family 3 (Camilot et al):
8 heterozygous patients
Calebiro et al:
four unrelated heterozygous patients
Vigone et al. 2 families C41S
Clinical Features:
Family 1 - Pedigree 1 (de Roux et al.):
diagnosis:
II/1: neonatal, euthyroid hyperthyrotropinaemia, normal gland on 123-I scan, normal Tg levels
Family 2 - Pedigree 2 (Alberti et al.):
diagnosis:
II/2: neonatal, euthyroid hyperthyrotropinaemia, normal gland on ultrasound, normal 99mTc scan,
I/1: elevated TSH levels
Family 3 (Camilot et al.):
8 patients with subclinical hypothyroidism in three non-related families
Calebiro et al.:
age at diagnosis: 3d, 41d, 5 months, 5yr
Vigone et al. 2 unrelated families, (siblings with heterozygous mutation, no parental data thus familial assumed)
diagnosis:
II/1: neonatal, euthyroid hyperthyrotropinaemia, normal gland on 123-I scan, normal Tg levels
Family 2 - Pedigree 2 (Alberti et al.):
diagnosis:
II/2: neonatal, euthyroid hyperthyrotropinaemia, normal gland on ultrasound, normal 99mTc scan,
I/1: elevated TSH levels
Family 3 (Camilot et al.):
8 patients with subclinical hypothyroidism in three non-related families
Calebiro et al.:
age at diagnosis: 3d, 41d, 5 months, 5yr
Vigone et al. 2 unrelated families, (siblings with heterozygous mutation, no parental data thus familial assumed)
Treatment:
default
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
0
6
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:
De Roux et al.
J. Clin. Endocrinol. Metabol. 81: 4229-4235
Four families with loss of function mutations of the thyrotropin receptor
1996
Reference 2:
Alberti et al.
J. Clin. Endocrinol. Metab. 87: 2549-2555
Germline Mutations of TSH Receptor Gene as Cause of Nonautoimmune Subclinical Hypothyroidism
2002
Reference 3:
Camilot et al.
Clin Endocrinol (Oxf) 63:146-151.
Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes.
2005
Reference 4:
Lábadi, Árpád, et al.
The Journal of Clinical Endocrinology & Metabolism
Loss-of-function variants in a Hungarian cohort reveal structural insights on TSH receptor maturation and signaling
2015
Reference 5:
Vigone et al.
Clinical Endocrinology
Mild TSH resistance: Clinical and hormonal features in childhood and adulthood
2017