Table 1. [Mutations in the Beta Subunit Gene Responsible for Congenital Isolated Central Hypothyroidism]. - Endotext

Mutation of TSHB	Consequence of mutation on TSH heterodimer formation
G29R (31)	Prevents dimer formation modifying the CAGYC region
E12X (33)	Truncated TSH beta subunit unable to associate with alpha chain
C105V, 114X (41)	Destruction of a disulfide bond, non-homologous carboxyterminus. Change of amino acid sequence in the “seat belt” region leads to unstable heterodimer
Q49X (37)	Truncated TSH beta subunit forming a bio-inactive heterodimer with the alpha chain
IVS2+5→A (39)	Base substitution at intron 2 (position +5) with shift of the translational start point to an out of frame position of exon 3 resulting in a truncated transcript
C85R (43)	T to C transition at codon 85 of exon 3 resulting in a change of cysteine to arginine, preventing the formation of a functional heterodimer with the alpha subunit
C162G→A (12)	G to A change at the 5’ donor splice site of exon/intron 2 transition causing a (CGA→CGG) polymorphism, which although per se silent, disrupts the 5’ consensus sequence critical for splicing and causes complete skipping of exon 2
C88Y (12)	323G>A transition resulting in a C88Y change. This cysteine residue is conserved among all pituitary and placental glycoprotein hormone-beta subunits and the loss alters the conformation and intracellular degradation

Mutation of TSHB

Consequence of mutation on TSH heterodimer formation

G29R (31)

Prevents dimer formation modifying the CAGYC region

E12X (33)

Truncated TSH beta subunit unable to associate with alpha chain

C105V, 114X (41)

Destruction of a disulfide bond, non-homologous carboxyterminus. Change of amino acid sequence in the “seat belt” region leads to unstable heterodimer

Q49X (37)

Truncated TSH beta subunit forming a bio-inactive heterodimer with the alpha chain

IVS2+5→A (39)

Base substitution at intron 2 (position +5) with shift of the translational start point to an out of frame position of exon 3 resulting in a truncated transcript

C85R (43)

T to C transition at codon 85 of exon 3 resulting in a change of cysteine to arginine, preventing the formation of a functional heterodimer with the alpha subunit

C162G→A (12)

G to A change at the 5’ donor splice site of exon/intron 2 transition causing a (CGA→CGG) polymorphism, which although per se silent, disrupts the 5’ consensus sequence critical for splicing and causes complete skipping of exon 2

C88Y (12)

323G>A transition resulting in a C88Y change. This cysteine residue is conserved among all pituitary and placental glycoprotein hormone-beta subunits and the loss alters the conformation and intracellular degradation

From: Physiology of the Hypothalamic-Pituitary-Thyroid Axis

Endotext [Internet].

Feingold KR, Anawalt B, Blackman MR, et al., editors.

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