AI Article Synopsis
- The study investigates TRPV6 as a gene linked to chronic pancreatitis (CP) and finds it associated with calcium (Ca) dysregulation.
- Researchers analyzed TRPV6 in various CP patient groups, identifying 25 rare TRPV6 variants, with 18 being newly reported.
- The analysis indicates that functionally deficient TRPV6 variants are more common in hereditary and familial CP, often co-occurring with other known risk genes, and highlight their significant role in the disease.
Article Abstract
The recent discovery of TRPV6 as a pancreatitis susceptibility gene served to identify a novel mechanism of chronic pancreatitis (CP) due to Ca dysregulation. Herein, we analyzed TRPV6 in 81 probands with hereditary CP (HCP), 204 probands with familial CP (FCP), and 462 patients with idiopathic CP (ICP) by targeted next-generation sequencing. We identified 25 rare nonsynonymous TRPV6 variants, 18 of which had not been previously reported. All 18 variants were characterized by a Ca imaging assay, with 8 being identified as functionally deficient. Evaluation of functionally deficient variants in the three CP cohorts revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Our findings confirm that functionally deficient TRPV6 variants represent an important contributor to CP. Importantly, functionally deficient TRPV6 variants account for a significant proportion of cases of HCP/FCP.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/humu.24315 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Among the Masses: Multiple Left Atrial Undifferentiated Pleomorphic Sarcomas.
Ochsner J
January 2024
Division of Cardiology, Baylor Scott & White Medical Center, Temple, TX.
Undifferentiated pleomorphic sarcoma, an exceedingly rare and aggressive primary cardiac tumor arising from mesenchymal stem cells, is associated with poor prognosis and high mortality despite adequate treatment. A 52-year-old female presented with a 2-month history of angina and dyspnea on exertion. Her clinical history included severe acute respiratory syndrome coronavirus 2 myocarditis and iron deficiency anemia.
View Article and Find Full Text PDFBiallelic variants in the cause mitochondrial respiratory complex assembly defects associated with Leigh syndrome in probands.
Mol Genet Metab Rep
December 2024
Eye Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Background: Variants in have been reported to be associated with Leigh syndrome. However, further expansion of the -phenotype and variants spectrum of -related Leigh syndrome are still required.
Methods: Two patients diagnosed with Leigh syndrome were recruited, and whole-exome sequencing was performed to identify the genetic variants responsible for the abnormal gait, dystonia, and bilateral basal ganglia lesions, followed by validation using Sanger sequencing.
Efficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.
Front Immunol
December 2024
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.
View Article and Find Full Text PDFDecoding the prognostic landscape of LUAD: the interplay between N-methyladenosine modification and immune microenvironment.
Front Immunol
December 2024
State Key Laboratory of Trauma and Chemical Poisoning, Department of Stem Cell and Regenerative Medicine, Daping Hospital, Army Medical University, Chongqing, China.
Background: To determine the role of N-methyladenosine (mA) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).
Methods: Consensus clustering was performed to identify the subgroups with distinct immune or mA modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays.
Depression of Ca1.2 activation and expression in mast cells ameliorates allergic inflammation diseases.
J Pharm Anal
November 2024
Department of Pharmaceutical Analysis, School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, China.
Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca level, but the intake and effects of the intracellular Ca remain unclear. The Ca influx is controlled by members of Ca channels, among which calcium voltage-gated channel subunit alpha1 C (Ca1.2) is the most robust.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!