Objective: To study the effect of genistein(Gen) on expression of monocyte chemotactic protein-1 ( MCP-1) mRNA and MCP-1 induced by oxidized low density lipoprotein (ox-LDL) in human umbilical venous smooth mulscle cells (hUVSMC). Methods: Gen at different doses (1.0?10-5、3.0?10-5、9.0?10-5mol/L) were used to observe the effect on expression of MCP-1 mRNA and MCP-1 induced by ox-LDL in hUVSMC cultures and compared with the effect of 17b-estradiol(17b-E). RT-PCR and ELISA were used to measure expression of MCP-1 mRNA and MCP-1 respectively. Results: Gen significantly inhibited the expression of MCP-1 mRNA and MCP-1 in cell culture supernant . There was no significant difference in the inhibitory effect between high concentration of Gen and physiological level of 17b-E . Conclusion: Gen can down-regulate hUVSMC expression of MCP-1 mRNA and MCP-1. It suggests that this may be the important antiatherogenic mechanism of Gen.

OBJECTIVE: To study the effect of hesperidin and rutin on oxidative modification of high density lipoprotein (HDL) in vitro. METHODS: HDL was isolated from healthy human plasma by sequential ultracentrifugation, and was oxidized by copper ions. The inhibitory effects of hesperidin and rutin on HDL oxidative modification were valued by the formation of malondialdehyde (MDA). RESULTS: Hesperidin and rutin significantly inhibited copper-induced oxidation of HDL in a dose-dependent manner. CONCLUSION: Both hesperidin and rutin can prevent HDL from copper-induced oxidative modification in vitro. This result suggests that they might have antiatherogenic effect.

Objective To evaluate the antioxidant effect of hesperidin and its effect on transcription of monocyte chemoattractant protein 1 (MCP 1) in rabbits with dietary atherosclerotic lesions. Methods (1) Low density lipoprotein (LDL) was isolated from healthy human plasma by sequential ultra centrifugation and oxidized by copper. The contents of malondialdehyde (MDA) were measured at different dosages of the drug and at different reaction time. (2) Atherosclerotic model of rabbits was established by feeding rabbits with high lipid diet and immune injury. A total of 18 rabbits were divided randomly into three groups: control group, model group, and hesperidin group ( n =6 in each group). Rabbits in the control group were fed with common diet, those in the model group with high lipid diet, and those in the hesperidin group with high lipid diet plus hesperidin. After 10 experimental weeks, blood samples were collected from the marginal ear veins for the detection of the contents of MDA and nitric oxide (NO). The rabbits were sacrificed for the isolation of the thoracic aorta. MCP 1 mRNA transcription in the thoracic aorta was detected by RT PCR. Results Hesperidin could significantly inhibit MDA production in a dose dependent manner in vitro ( P

OBJECTIVE To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis (HME). METHODS For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. RESULTS A novel heterozygous frameshift mutation c.1202delT (p.I401Tfs*2)was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. CONCLUSION A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

OBJECTIVETo analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.

METHODSNeuropsychological profile of the child was analyzed. Color Doppler, CT and MRI were used for detecting the nodules in the body. Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities.

RESULTSThe child had mental retardation, maxillofacial dysmorphism on the right side, and irregular solid nodules on the back. The karyotypes of the child and his parents were all normal, while aCGH has identified a de novo constitutive 1.2 Mb deletion at 17q11.2 in the child. The aCGH results of his parents were normal.

CONCLUSIONThe de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.

Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; Comparative Genomic Hybridization ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Maxillofacial Abnormalities ; genetics ; Phenotype ; Smith-Magenis Syndrome ; genetics

OBJECTIVETo detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome.

METHODSPeripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Plasma level of B-cell activating factor (BAFF) was also determined for all family members.

RESULTSA hemizygous mutation (c.257G>A) of the WAS gene was identified in all patients from the family, for which the patient's mother was heterozygous. The same mutation was not found among healthy members of the family. Compared with unaffected members, all patients had a higher level of BAFF.

CONCLUSIONThe c.257G>A mutation of the WAS gene probably underlies the Wiskott-Aldrich syndrome in this family.

B-Cell Activating Factor ; blood ; Child, Preschool ; Heterozygote ; Humans ; Male ; Mutation ; Wiskott-Aldrich Syndrome ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To carry out prenatal diagnosis for a fetus with ultrasonographic abnormality. METHODS: Chromosomal karyotyping and array comparative genomic hybridization (array-CGH) analysis were applied for the diagnosis. Peripheral blood samples were also taken from the parents for chromosome karyotyping analysis. RESULTS: The fetal karyotype showed additional material of unknown-origin attached to Yq. Array CGH analysis confirmed that the material was derived from 3q22.1q29. The father was found to carry a balanced translocation 46, X, t(Y;3)(q12;q23) (which was diagnosed as 46,XY,Y≥18 elsewhere), whilst the mother was found to be normal. CONCLUSION 3q partial trisomy may present as malformation of multiple systems. Combination of chromosome karyotyping and array-CGH can provide reliable diagnosis for fetuses with abnormalities by ultrasonography.
Chromosomes, Human, Pair 3 ; genetics ; Comparative Genomic Hybridization ; Female ; Fetus ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Trisomy

OBJECTIVE: To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS). METHODS: Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members. RESULTS: No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion. CONCLUSION The loss of the MAGED2 gene may underlie the BS in this pedigree.
Adaptor Proteins, Signal Transducing ; genetics ; Antigens, Neoplasm ; genetics ; Bartter Syndrome ; genetics ; Female ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Sequence Deletion

OBJECTIVE: To analyze the clinical features and genetic mutations in a patient with mucolipidosis type II α/β by using next generation sequencing. METHODS: Clinical data of the patient was collected. Genomic DNA of the patient and her parents was extracted by a standard method. The patient was subjected to targeted sequencing using an Ion Ampliseq panel, which included genes related to mucolipidosis and mucopolysaccharidosis. Suspected mutations were verified by Sanger sequencing. RESULTS: Compound heterozygous mutations, namely c.1284+1G>T and c.1090C>T (p.Arg364*), were detected in the patient, which were respectively inherited from her mother and father. No other disease-causing mutation was detected in the patient. GNPTAB c.1090C>T was known to be pathogenic, while GNPTAB c.1284+1G>T is a novel mutation. The same mutations were not detected among 50 healthy controls. CONCLUSION The compound heterozygous mutations c.1284+1G>T and c.1090C>T (p.Arg364*) of GNPTAB gene probably account for the mucolipidosis type II α/β in the patient. NGS has a great value for the molecular diagnosis and typing of mucolipidosis.
Female ; High-Throughput Nucleotide Sequencing ; Humans ; Mucolipidoses ; genetics ; Mutation ; Transferases (Other Substituted Phosphate Groups) ; genetics