Novel Mutations in the 3β-hydroxy-Δ5-C27-steroid Dehydrogenase Gene (HSD3B7) in a Patient with Neonatal Cholestasis

Huang, Heyu; Zhou, Hua; Hong, Wang; Chen, Yaxian; Fang, Feng

doi:10.4103/0366-6999.172603

Cited by 12 publications

(16 citation statements)

References 6 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As illustrated in Figure 2F, the region where rs1549293 resides was a potential enhancer as shown by its H3K4Me1 and H3K27Ac modification from ENCODE data [32].We then searched DNase I hypersensitive sites (DHSs), which showed possible transcription activities in the genome, across a total of 79 cell types [33]. In the genomic locus covering rs1549293, the chromosomal interactions with FUS and HSD3B7 were observed to form each of 54 kb and 145 kb complexes, suggesting a regulatory role by this SNP to these obesity-associated genes (Figure 2F, Pearson correlation coefficient r is 0.78 and 0.74, respectively) [34], [35]. Supporting evidence also came from the polymerase II chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) data [36], which suggested that rs1549293 located in an enhancer that regulated the activities of both promoters of FUS and HSD3B7 .…”

Section: Resultsmentioning

confidence: 98%

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a “comfort” zone for a high frequency of 677T between latitudes of 35–45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

show abstract

Section: Resultsmentioning

confidence: 98%

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

show abstract

“…Progressive intrahepatic cholestasis and neonatal cholestasis can be caused by several mutations in the HSD3B7 gene (54). Bile acid therapy is effective in treating HSD3B7deficient patients.…”

Section: Inborn Errors Of Bile Acid Metabolismmentioning

confidence: 99%

Bile Acids as Metabolic Regulators and Nutrient Sensors

2019

View full text Add to dashboard Cite

Bile acids facilitate nutrient absorption and are endogenous ligands for nuclear receptors that regulate lipid and energy metabolism. The brain–gut–liver axis plays an essential role in maintaining overall glucose, bile acid, and immune homeostasis. Fasting and feeding transitions alter nutrient content in the gut, which influences bile acid composition and pool size. In turn, bile acid signaling controls lipid and glucose use and protection against inflammation. Altered bile acid metabolism resulting from gene mutations, high-fat diets, alcohol, or circadian disruption can contribute to cholestatic and inflammatory diseases, diabetes, and obesity. Bile acids and their derivatives are valuable therapeutic agents for treating these inflammatory metabolic diseases.

show abstract

“…Among the prognostic differentially expressed mRNAs, HSD3B7 encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily [ 38 ]. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, but reduces the risk of late-onset Parkinson’s disease [ 39 , 40 ]. 7α25HC, an intermediate product of bile acid synthesis, is degraded by HSD3B7.…”

Section: Discussionmentioning

confidence: 99%

Analyzing the lncRNA, miRNA, and mRNA-associated ceRNA networks to reveal potential prognostic biomarkers for glioblastoma multiforme

et al. 2020

View full text Add to dashboard Cite

Background: Glioblastoma multiforme (GBM) is the most seriously brain tumor with extremely poor prognosis. Recent research has demonstrated that competitive endogenous RNA (ceRNA) network which long noncoding RNAs (lncRNAs) act as microRNA (miRNA) sponges to regulate mRNA expression were closely related to tumor development. However, the regulatory mechanisms and functional roles of ceRNA network in the pathogenesis of GBM are remaining poorly understood. Methods: In this study, we systematically analyzed the expression profiles of lncRNA and mRNA (GSE51146 dataset) and miRNA (GSE65626 dataset) from GEO database. Then, we constructed a ceRNA network with the dysregulated genes by bioinformatics methods. The TCGA and GSE4290 dataset were used to confirm the expression and prognostic value of candidate mRNAs. Results: In total, 3413 differentially expressed lncRNAs and mRNAs, 305 differentially expressed miRNAs were indentified in GBM samples. Then a ceRNA network containing 3 lncRNAs, 5 miRNAs, and 60 mRNAs was constructed. The overall survival analysis of TCGA databases indicated that two mRNAs (C1s and HSD3B7) were remarkly related with the prognosis of GBM. Conclusion: The ceRNA network may increase our understanding to the pathogenesis of GBM. In general, the candidate mRNAs from the ceRNA network can be predicted as new therapeutic targets and prognostic biomarkers for GBM.

show abstract

Novel Mutations in the 3β-hydroxy-Δ5-C27-steroid Dehydrogenase Gene (HSD3B7) in a Patient with Neonatal Cholestasis

Cited by 12 publications

References 6 publications

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

Bile Acids as Metabolic Regulators and Nutrient Sensors

Analyzing the lncRNA, miRNA, and mRNA-associated ceRNA networks to reveal potential prognostic biomarkers for glioblastoma multiforme

Contact Info

Product

Resources

About