A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations

Sun, Jianhua; Sun, Lizhi; Chen, Weijie; Yin, Xiaolin; Lu, Yong; Jiang, Qiang

doi:10.3892/mmr.2018.9499

Cited by 3 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The receptor itself binds to APOB, mediating the endocytosis of the lipids of the lipoprotein. A mutation in APOBR has been associated with hypothyroidism [52]. APOBR is known as a macrophage receptor but is known to be expressed in the brain [53], and cholesterol metabolism and transport are often implicated in neurological disease [54].…”

Section: Resultsmentioning

confidence: 99%

RNA-sequencing of human post-mortem hypothalamus and nucleus accumbens identifies expression profiles associated with obesity

Wake

Schneider

Stein

et al. 2022

Preprint

View full text Add to dashboard Cite

Obesity, the accumulation of body fat to excess, may cause serious negative health effects, including increased risk of heart disease, type 2 diabetes, stroke and certain cancers. The biology of obesity is complex and not well understood, involving both environmental and genetic factors and affecting metabolic and endocrine mechanisms in tissues of the gut, adipose, and brain. Previous RNA sequencing studies have identified transcripts associated with obesity and body mass index in blood and fat, often using animal models, but RNA sequencing studies in human brain tissue related to obesity have not been previously undertaken. We conducted both large and small RNA sequencing of hypothalamus (207 samples) and nucleus accumbens (276 samples) from individuals defined as consistently obese (124 samples), consistently normal weight as controls (148 samples) or selected without respect to BMI and falling within neither case nor control definition (211 samples), based on longitudinal BMI measures. The samples were provided by three cohort studies with brain donation programs; the Framingham Heart Study (FHS), the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). For each brain region and large/small RNA sequencing set, differential expression of obesity, BMI, brain region and sex was performed. Analyses were done transcriptome-wide as well as with a priori defined sets of obesity or BMI-associated mRNAs and microRNAs (miRNAs). There are sixteen mRNAs and five microRNAs that are differentially expressed (adjusted p < 0.05) by obesity or BMI in these tissues, several of which were validated with qPCR data. The results include many that are BMI-associated, such as APOBR and CES1, as well as many associated with the immune system and some with addiction, such as the gene sets 'cytokine signaling in immune system' and 'opioid signaling'. In spite of the relatively large number of samples, our study was likely under-powered to detect other transcripts or miRNA with relevant but smaller effects.

show abstract

Section: Resultsmentioning

confidence: 99%

RNA-sequencing of human post-mortem hypothalamus and nucleus accumbens identifies expression profiles associated with obesity

Wake

Schneider

Stein

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC [ 27 ]. WES technology is an effective method for identifying potential causative genes in disease phenotypes [ 28 ]. In the present study, WES was performed to identify potential causative genes in the patient who was diagnosed with UC associated with PSC and SSA.…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA

Chen

Shi

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

View full text Add to dashboard Cite

Background. Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. Methods. DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). Results. In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs ∗ 15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA. Conclusions. The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs ∗ 15) mutation may be associated with SSA in this patient.

show abstract

“…While CCDC57 and SLC16A3 are highly expressed in thyroid and pancreas, the expression of FASN is almost absent in these two tissues (Figure 8a,b,c). FASN, which plays critical role in de novo synthesis of fatty acids, is critically important for proper liver function and is highly expressed in liver (45) (Figure 8a). However, FASN is linked to dysregulation of thyroid and is strongly associated with hypothyroidism (45) at the same time.…”

Section: Tre Functional Duality In Regulatory Locus Encapsulationmentioning

confidence: 99%

Bimodal sequence composition underlies functional duality of transcribed enhancers

Flores¹,

Ovcharenko

2020

Preprint

View full text Add to dashboard Cite

Background:Recent studies have drawn attention to transcribed enhancers (trEs) as important regulatory elements of gene expression; however, their characteristics and mechanisms of action remain poorly understood. Results:We profiled the characteristics of trEs and obtained insights into their mechanisms of action. We found that trEs harbor functional duality related to bimodal sequence composition. TrEs are composed of nonoverlapping cores and flanking regions (flanks): cores function as regular enhancers, while flanks transcribe enhancer RNAs (eRNAs) that can potentially regulate the expression of their target genes in trans. Cores are evolutionarily conserved and compact, while flanks are significantly longer. We observed that approximately 25% of eRNAs transcribed from the flanks likely contribute to trans DNA:RNA triple helix formation, while another 10% likely employ classical mechanisms of RNA-based regulation. We found that the majority of human enhancers are not transcribed, and trEs are strikingly different from regular enhancers in their functional characteristics. In addition, we found evidence for trEs exhibiting functional duality in regulatory locus encapsulation (RLE), effectively providing localized control over the spread of gene expression upregulation by trE cores and other locus enhancers. Conclusions:In summary, our results advocate for enhancer transcription being an uncommon mechanism of gene regulation, and the duality of transcribed enhancer function being a product of additive, not overlapping, DNA sequence encryption.

show abstract

A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations

Cited by 3 publications

References 43 publications

RNA-sequencing of human post-mortem hypothalamus and nucleus accumbens identifies expression profiles associated with obesity

RNA-sequencing of human post-mortem hypothalamus and nucleus accumbens identifies expression profiles associated with obesity

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA

Bimodal sequence composition underlies functional duality of transcribed enhancers

Contact Info

Product

Resources

About