The decrease of T3 / T4 is not hypothyroidism - a new mutation of Serpina7 gene results in partial thyroglobulin...

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Thyroxine-Binding Globulin (TBG) is crucial for thyroid hormone transport.
• Decreased levels of total T3 and T4 can be caused by various factors, including genetic mutations.
• Misinterpreting these changes can lead to unnecessary medical interventions.

Purpose of the Study:

• To investigate a rare genetic cause of decreased T3 and T4 levels within a family.
• To identify a specific mutation in the TBG gene responsible for these hormonal changes.
• To provide guidance for accurate diagnosis and prevent overtreatment.

Main Methods:

• Hormone levels (TSH, total T4, T3, free T4, free T3) were measured using chemiluminescence immunoassay.
• Direct DNA sequencing was employed to identify mutations in the TBG gene.
• In vitro expression studies were conducted to assess the functional impact of the identified mutation.

Main Results:

• A frameshift mutation (c.1114delc, p. l372ffs * 32) was identified in the TBG gene of the affected family members.
• The proband was heterozygous for this mutation.
• In vitro studies confirmed that the mutated TBG exhibited reduced affinity for T4, leading to decreased total T3 and T4 levels while free T3, free T4, and TSH remained normal.

Conclusions:

• A novel TBG gene mutation can cause decreased total T3 and T4 with normal TSH, FT3, and FT4.
• Identifying TBG deficiency through genetic testing is essential for patients presenting with low total thyroid hormones but normal TSH.
• This diagnosis prevents misdiagnosis and inappropriate treatment for thyroid dysfunction.