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Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B (encoding a copper-transporting P-type ATPase) variants that shows various characteristics according to race and geographical region. This study was aimed to provide a comprehensive analysis of ATP7B variants in China and to investigate a plausible role of common variants in WD manifestations. Methods: A total of 1366 patients (1302 index patients and 64 siblings) clinically diagnosed with WD (Leipzig score ≥ 4) were recruited. They underwent ATP7B gene sequencing and information of age and symptoms at onset was collected. The genotype–phenotype correlation was assessed in the index patients who were examined with two pathogenic variants and onset with hepatic (n = 276) or neurologic (n = 665) symptoms. Results: We identified 294 potentially pathogenic ATP7B variants (112 truncating, 174 missense, 8 in-frame) in the 1302 index patients, including 116 novel variants. The most frequent variant was c.2333G>T (R778L, allele frequency: 28.96%), followed by c.2975C>T (P992L, 13.82%), c.2621C>T (A874V, 5.99%), c.2755C>G (R919G, 2.46%), and c.3646G>A (V1216M, 1.92%). In 1167 patients, both pathogentic variants were identified, of which 532 different variant combinations were found. By binary logistic regression analysis, the factor associated with neurological presentation was high age-at-onset, but not sex, protein-truncating variant (PTV), or the common missense variants (R778L, P992L, and A874V). In the neurological group, low age-at-onset was a factor associated with dystonia, gait abnormality, and salivation; high age-at-onset was a factor associated with tremor; and the sex, low age-at-onset and A874V were independent factors associated with dysarthria. In addition, PTV, R778L, and P992L were predominant in early-onset patients, whereas A874V was predominant in late-onset patients, and patients with R778L/A874V genotype displayed a higher age-at-onset than patients with R778L/R778L or R778L/P992L genotype. Conclusions: Our work expanded the ATP7B variant spectrum and highlighted the differences among patients with WD in age-at-onset and ATP7B variants, which may provide some valuable insights into the diagnosis, counseling, and treatment of patients with WD. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B (encoding a copper-transporting P-type ATPase) variants that shows various characteristics according to race and geographical region. This study was aimed to provide a comprehensive analysis of ATP7B variants in China and to investigate a plausible role of common variants in WD manifestations. Methods: A total of 1366 patients (1302 index patients and 64 siblings) clinically diagnosed with WD (Leipzig score ≥ 4) were recruited. They underwent ATP7B gene sequencing and information of age and symptoms at onset was collected. The genotype–phenotype correlation was assessed in the index patients who were examined with two pathogenic variants and onset with hepatic (n = 276) or neurologic (n = 665) symptoms. Results: We identified 294 potentially pathogenic ATP7B variants (112 truncating, 174 missense, 8 in-frame) in the 1302 index patients, including 116 novel variants. The most frequent variant was c.2333G>T (R778L, allele frequency: 28.96%), followed by c.2975C>T (P992L, 13.82%), c.2621C>T (A874V, 5.99%), c.2755C>G (R919G, 2.46%), and c.3646G>A (V1216M, 1.92%). In 1167 patients, both pathogentic variants were identified, of which 532 different variant combinations were found. By binary logistic regression analysis, the factor associated with neurological presentation was high age-at-onset, but not sex, protein-truncating variant (PTV), or the common missense variants (R778L, P992L, and A874V). In the neurological group, low age-at-onset was a factor associated with dystonia, gait abnormality, and salivation; high age-at-onset was a factor associated with tremor; and the sex, low age-at-onset and A874V were independent factors associated with dysarthria. In addition, PTV, R778L, and P992L were predominant in early-onset patients, whereas A874V was predominant in late-onset patients, and patients with R778L/A874V genotype displayed a higher age-at-onset than patients with R778L/R778L or R778L/P992L genotype. Conclusions: Our work expanded the ATP7B variant spectrum and highlighted the differences among patients with WD in age-at-onset and ATP7B variants, which may provide some valuable insights into the diagnosis, counseling, and treatment of patients with WD. [ABSTRACT FROM AUTHOR]

Background: In recent years, the relationship between thyroid stimulating hormone (TSH) and obesity has been widely discussed. However, it is unclear how thyroid hormone concentrations relate to body weight and its impact on metabolic risk markers. This study aimed to assess how thyroid function is linked to underweight, overweight, or obesity, and metabolic risk markers in adults. Methods: A total of 16,975 subjects, aged 18–80 years, who attended the Health Management Center of Tongji Hospital, Wuhan, China were enrolled in this study. Anthropometric and laboratory data were collected and analyzed. Results: Serum free triiodothyronine (fT3) and fT3/free thyroxine (fT4) ratio (fT3/fT4) were positively associated with body mass index (BMI) (P < 0.001), while there was a negative relationship between fT4 and BMI (P < 0.001) according to multivariable regression analysis adjusted for age and sex. Associations between thyroid hormone concentrations and markers of blood pressure, and lipid and glucose metabolism were identified after adjustment for age, sex, and BMI, with TSH being negatively associated with fasting blood glucose (FBG). fT3 was positively associated with systolic blood pressure and low-density lipoprotein-cholesterol, while fT4 was positively associated with diastolic blood pressure, FBG, and high-density lipoprotein-cholesterol (HDL-C), and negatively associated with hemoglobin A1c (HbA1c) and triglyceride. Finally, fT3/fT4 was positively associated with HbA1c and triglyceride, and negatively associated with HDL-C. Conclusions: Overweight or obese participants had a high serum concentration of fT3, high fT3/fT4 ratio, and a low concentration of fT4. Underweight participants had high concentrations of fT4 and low concentrations of fT3. Thus, relationships between thyroid hormones and metabolic risk markers were identified which suggest that thyroid function might be one factor that influences body weight and the co-morbidities of obesity. [ABSTRACT FROM AUTHOR]