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Cross-Sectional Variations within Composition and Function regarding Coral formations Deep sea Microbiome Together with Community Anthropogenic Impacts for the Kenyan Coast with the Indian Marine.
BACKGROUND AND PURPOSE Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. EXPERIMENTAL APPROACH Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomised rat model and in CKD patients. KEY RESULTS Six aryl-containing metabolites (ACM) were significantly increased from week 1 to week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2, and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy, and immunoglobulin A nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly upregulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR shRNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. CONCLUSION AND IMPLICATIONS We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment. This article is protected by copyright. All rights reserved.OBJECTIVE To explore the genetic basis for a female with a peripheral lymphocyte karyotype of trisomy 18 but normal intelligence. METHODS G-banding karyotype analysis, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism microarray (SNP array) were employed to analyze the peripheral blood sample and buccal cells from the patient. RESULTS Chromosomal karyotyping, SNP array and FISH analysis of the patient's peripheral blood all suggested 47,XX,+18. Interphase FISH analysis of buccal cells, however, revealed presence of 45,X and low percentage of trisomy 18 and monosomy 18. CONCLUSION The clinical manifestation of germ layer chromosomal mosaicism is complex. The impact of the genetic disorder on the individual will depend on the structure and function derived from the affected germ layer.OBJECTIVE To carry out genetic testing for a male infant suspected for Menkes disease. METHODS Genomic DNA of the proband and his parents were extracted and subjected to family trio whole exome sequencing (WES). Microduplication and microdeletion of the ATP7A gene were detected by multiplex ligation-dependent probe amplification (MLPA). Suspected variants were subjected to bioinformatic analysis and verified by Sanger sequencing. RESULTS The proband was found to harbor a de novo c.1870 -13T>G variation of the ATP7A gene, which may alter a splice site and affect its protein product. CONCLUSION The patient was diagnosed with Menkes disease due to the c.1870 -13T>G variant of the ATP7A gene. Whole exome sequencing of family trios is a powerful tool for the diagnosis of diseases with strong phenotypic heterogeneity.OBJECTIVE To explore the genetic basis for a child with supravalvular aortic stenosis. METHODS The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings. CONCLUSION The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.OBJECTIVE To explore the genetic basis for a fetus with cleft lip and palate. METHODS Copy number variations (CNVs) in the fetus and his parents were detected with chromosomal microarray analysis (CMA). RESULTS As revealed by the CMA assay, the fetus has carried a 228 kb deletion in Xp11.22 region and a 721 kb duplication in 9p21.1. Both CNVs were inherited from the parents. The CNV in Xp11.22 was predicted to be pathogenic by involving the PHF8 gene, whilst the CNV in 9p21.1 was predicted to be benign. CONCLUSION Deletion of the Xp11.22 region probably underlies the cleft lip and palate in this fetus.OBJECTIVE To explore the genetic basis for a Chinese pedigree affected with split hand/foot malformation (SHFM). METHODS Genomic DNA of the proband and other affected members was extracted from peripheral blood samples. Chromosomal microarray analysis was employed to detect genome-wide copy number variations (CNVs). RESULTS A 400 kb microduplication was identified in the 10q24.31-q24.32 region among all affected individuals. The microduplication has involved four genes, namely LBX1, BTRC, POLL and DPCD, in addition with part of FBXW4 gene. CONCLUSION The 10q24.31-q24.32 microduplication has segregated with the disease phenotype in this pedigree and probably underlay the SHFM malformation in the patients.OBJECTIVE To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology. METHODS Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs. RESULTS Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal. CONCLUSION The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.OBJECTIVE To explore the genetic basis for a child featuring delayed intellectual development. METHODS The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents. RESULTS No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8. CONCLUSION The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.OBJECTIVE To explore the clinical characteristics and genetic variants in a child with tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay. METHODS Clinical feature of the patient was summarized. Genomic DNA was extracted from peripheral blood samples taken from the child and her family members. All exons of GCH1, TH and SPR genes were subjected to targeted capture and next-generation sequencing. Suspected variants were verified by Sanger sequencing. RESULTS The child could not sit alone at 7 month and 11 days. Physical examination suggested motor retardation and hypotonia, limb stiffness, head nodding, slight torticollis, and language and intellectual developmental delays. She developed involuntary shaking of limbs at 3 month old, which lasted approximately 10 seconds and aggregated with excitement and before sleeping. Cranial MRI revealed widening of subarachnoid space on the temporomandibular and particularly temporal sides. Genetic testing revealed that she has carried a nonsense c.457C>T (p.R153X) variant, which was known to be pathogenic, and a novel missense c.720C>G (p.I240M) variant of the TH gene. The two variants were derived from her father and mother, respectively. CONCLUSION The child was diagnosed as tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay due to compound heterozygous variants of the TH gene. Above finding has enriched the spectrum of TH gene variants.OBJECTIVE To explore the clinical and genetic features of a patient with mental retardation. METHODS G-Banding chromosomal karyotyping and high-throughput sequencing was carried out for the child. Suspected variant was validated in his family by Sanger sequencing and bioinformatic analysis. RESULTS The patient was found to carry a de novo heterozygous c.4090G>T (p.Gly1364X) variant of the ASXL3 gene, which was known to predispose to Bainbridge-Ropers syndrome. CONCLUSION The nonsense c.4090G>T (p.Gly1364X) variant probably accounts for the disease in this patient.OBJECTIVE To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.OBJECTIVE To carry out genetic testing and prenatal diagnosis for a family affected with recessive dystrophic epidermolysis bullosa (RDEB). Rapamycin METHODS All exons of the COL7A1 gene and their flanking regions were subjected to PCR and Sanger sequencing. Suspected variant was validated in family members, based on which prenatal diagnosis was provided. RESULTS Sanger sequencing found that the proband has carried two variants of the COL7A1 gene, namely c.7289delC (p.Pro2430Glnfs*36) and c.7474C>T (p.Arg2492*), which were respectively derived from his mother and father. The same variants were not found among 100 healthy controls. By prenatal diagnosis, the fetus was found to have inherited the c.7474C>T (p.Arg2492*) variant from its father. CONCLUSION The pathogenic variants of the COL7A1 gene of the RDEB family were clarified, based on which prenatal diagnosis was provided.OBJECTIVE To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation. METHODS Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene. RESULTS The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree. CONCLUSION Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.
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