The patient, a 26-year-old female, was hospitalised for repeated palpitations, dizziness and shortness of breath for eight months and fatigue for ten days. The patient had no obvious inducement until eight months before admission, when she began to experience palpitations and shortness of breath, combined with paroxysmal swelling, and pain and discomfort in the anterior cervical area, which were subsequently relieved. The patient visited the local hospital for treatment. The serum examination findings are shown in Table 1.
A cardiac colour Doppler ultrasound examination indicated a slight prolapse of the anterior mitral valve, while the left ventricular systolic and diastolic functions were normal. Following treatment with Youjiale (50 ug qd), the symptoms of palpitations and shortness of breath were relieved, as were the swelling and pain in the neck. The patient subsequently purchased and continued to take the Youjiale (50 mg qd), and while their symptoms of palpitations and shortness of breath recurred, they were tolerable. Ten days prior to admission, the patient had no obvious inducement or symptoms such as dizziness, nausea, vomiting or headache. The patient improved on her own but presented weakness in the limbs (mainly in both lower limbs) and pain and discomfort in both knees. There was no visual acuity decline and no visual field defect. The serum examination findings are shown in Table 1.
Previous history of fibrocystic breast disease.
No history of hypertension.
No history of cerebral infarction and coronary heart disease.
No history of myocardial infarction.
No history of atrial fibrillation.
The details of the medical history of the patient were as follows: 
Meanwhile, the mother had congenital heart disease and had undergone heart surgery (details unknown), while the father, brother and sister exhibited a decrease in FT3, TT3, TT4 and RT3, with the decrease in TT3 and TT4 more significant. The TBG detections across all three family members were normal at a low level and indicated a family genetic tendency.
Serum T3, T4, FT3, FT4 and TSH levels were determined via electrochemiluminescence (Cobas 8000, Roche Diagnostics GmbH, Switzerland), with TBG determined via chemiluminescence (DPC2000, Siemens, Germany). The experimental procedure was as follows: 1) preparation of standards, reagents and samples prior to the experiment; 2) sample addition (standards and samples) (100 microL), incubation at 37 C for 1 h; 3) suctioning and discarding was performed, with detection solution A (100 microL) added, followed by incubation at 37 C for 1 h; 4) plate washing was performed three times; 5) detection solution B (100 microL) was added prior to incubation at 37 C for 30 min; 6) plate washing was performed five times; 7) the substrate was added (100 microL), followed by incubation at 37 C for 10 min; 8) the reading was performed. Thyroid function tests were performed on the proband and their family members.
The human genomic DNA was extracted from peripheral blood leukocytes using a standard phenol-chloroform method. The coding region of the Serpina7 gene (exons 1-4) and exon-intron junction of the proband's family members were directly sequenced. In addition, the coding region of the Serpina7 gene (exons 1-4) and the exon-intron junction of 207 unrelated individuals were analysed through direct DNA sequencing and high-resolution melting (Tiangen Biotechnology Co., Ltd., Beijing, China).
The patient was examined using thyroid-related antibodies and thyroid colour Doppler ultrasound, among other methods, and common thyroid diseases, such as Hashimoto's thyroiditis, were excluded. A repeated examination of the thyroid function level showed the characteristics of a partial lack of TBG. Further gene sequencing revealed that the patient's Serpina7 gene locus was abnormal. Relevant literature was retrieved to analyse whether the abnormal locus was related to the decrease in TBG expression.
The keywords "thyroxine-binding globulin, gene and mutation" were used to search the literature in PubMed (biomedical literature database), Web of Science and other databases from their date of establishment to February 2022. A total of 45 studies were retrieved.