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Objective:To identify the causative gene in patients with familial progressive hyperpigmentation (FPH) .Methods:Two families with FPH were collected in March 2005 and March 2015 respectively, and their phenotypes were observed and recorded. The causative gene was investigated by single nucleotide polymorphism (SNP) -based genome-wide linkage analysis and exome sequencing, and verified by Sanger sequencing. The candidate gene expression was determined in FPH lesions and normal skin tissues by using immunohistochemical techniques.Results:The genome-wide linkage analysis showed that the causative gene in FPH family 1 was mapped to the loci of rs1026369-rs11857925 on chromosome 15q21.1 - q22.2; a disintegrin and metalloproteinase 10 (ADAM10) gene was identified as the possible causative gene by exome sequencing; Sanger sequencing showed that a splice-site mutation c.1511+1G>A in the ADAM10 gene was co-segregated with the disease phenotype in the FPH family 1. Immunohistochemical staining demonstrated that ADAM10 was expressed in both the FPH lesions and normal skin tissues of the proband in the FPH family 1. A missense mutation c.1172C>T (p.Ser319Phe) was identified by further ADAM10 mutation analysis in another 3-generation family with FPH (family 2). Both the above mutations were not detected in 300 local healthy controls.Conclusion:ADAM10 was identified as a novel causative gene responsible for FPH.
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Objective To study the inhibitory effects of tea flower extract(TFE) onα-glucosidase and glucose intestinal absor-ption. Methods Three different postprandial hyperglycemia models (2 g/kg glucose, 4 g/kg sucrose, and 6 g/kg starch) were used, with 8 mice in each group. Oral administration of 150 or 300 mg/kg of TFE, 6.25 mg/kg of acarbose, or water was performed on mice 1 day and 30 mins before the oral administration of 2 g/kg glucose, 4 g/kg sucrose, and 6 g/kg starch at 10 ml/kg of body weight. Blood glucose levels were analyzed chronologically to evaluate the effect of TFE. In vitro studies were also performed to study the inhibitory effects of TFE on α-glucosidase and small intestinal mucosa glycosidase. Results Neither TFE nor acarbose had significant influence in glucose-treated mice. However, there was a significant decrease in the postprandial blood glucose 20 min after sucrose administration (P<0.05), and 20 min and 40 min after starch administration (P<0.05). TFE also significantly inhibited the activities ofα-glucosidase of small intestinal mucosa, with 18.8%and 31.1%by 150 and 300 mg/kg TFE. The in vitro IC50 of TFE onα-glucosidase was 1.50 mg/ml. Conclusion TFE could effectively reduce the blood glucose level in hyperglycemic mice. Its mechanism might be related to the inhibitory effects ofα-glucosidase.