Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review

Molecular Genetics & Genomic Medicine, Journal Year: 2025, Volume and Issue: 13(4)

Published: April 1, 2025

ABSTRACT Background The ZNF526 gene encodes a ubiquitously expressed Kruppel‐type zinc finger protein crucial in transcriptional regulation. Recent studies suggest that biallelic pathogenic variants may lead to Dentici‐Novelli neurodevelopmental syndrome, characterized by microcephaly, developmental delay, epilepsy, and ocular anomalies. To date, phenotypic details have been reported for only six patients with variants. Methods This study gathered clinical information genetic data from child disorders. A three‐dimensional model was employed predict variant effects on structure. literature review conducted compare this case previously cases, analyzing features findings. Results proband, 7‐month‐old girl, exhibited limb hypotonia, abnormal brain imaging, seizures. Chromosomal karyotype analysis copy number variation analyses were normal. Whole exome sequencing revealed two heterozygous the (NM_133444.3): c.1426del (p.Val476Phefs*9), de novo frameshift variant, c.1513T;> C (p.Cys505Arg), inherited her mother. These unreported are separate alleles, forming compound state correlated presentation. Ocular anomalies absent, while café‐au‐lait spots represent novel feature. Among 12 cases of 11 unique identified, loss‐of‐function possibly linked Conclusion describes youngest patient broadening mutation spectrum detailing associated profile. findings valuable diagnosis family counseling syndrome.

Language: Английский

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A zinc finger protein shapes the temperature adaptability of a cosmopolitan pest

Open Biology, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

Global climate change is characterized by increased extreme temperatures affecting insects at all trophic levels. Zinc finger proteins (ZFPs) are key regulators of gene expression and cell differentiation in eukaryotes, essential for stress resistance both animals plants. Using CRISPR/Cas9 deletion, this study predicted examined the structure ZFP320 diamondback moth ( Plutella xylostella ) investigated its function temperature response through a comprehensive age-stage, two-sex life table analysis. We found encodes 387 amino acid protein (43 kDa) with no transmembrane domains, featuring ZnF-C2H2 domain. Quantitative fluorescence analysis showed that under high temperatures. knockout altered antioxidant expression, resulting higher levels superoxide dismutase catalase mutant strains compared wild-type strain. Life revealed had shorter fecundity oviposition periods normal Additionally, exhibited lower parameters r , λ R 0 ), as well reduced survival rates critical thermal maxima. Notably, PxZFP320 plays crucial role adaptation, paving way future investigations on significance ZFPs P. ’s tolerance.

Language: Английский

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Molecular Functions and Potential Utilization of Zinc Finger Proteins in Protozoan Parasites

Published: April 10, 2025

Zinc finger proteins (ZFP) are metalloproteins whose zinc atom interacts with side chains of specific histidines and cysteines the motif, generating functional three dimensional structures. A good number these from different species similar while others divergent in structure function. Existing literature on structural features, functions their potential to be targeted for drug development or used as molecular tools parasitic protozoa was explored. Evidence reviewed articles revealed that, just like other eukaryotes, function various parasite cellular processes such as: transcription, RNA editing, mRNA processing & export and, turn-over among others. Some them had same features homologues eukaryotes including hosts. However, there were which studies aiming at replacing reported positive results some parasites Giardia lamblia, Trichomonas vaginalis Leishmania donovani though this is promising, off- target challenge that can cause effects, must solved before wide application achieved. Successful engineering use genome editing also Plasmodium falciparum. Since nucleases a powerful research medical tool, repurposing ZFPs useful therapy discovery. For succeed, more knowledge how regulated needed.

Language: Английский

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ZNF473 as a novel prognostic biomarker and therapeutic target in colorectal adenocarcinoma: A comprehensive bioinformatics analysis

Asian Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Targeting RNA-protein interactions with small molecules: promise and therapeutic potential

Medicinal Chemistry Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 23, 2024

Abstract The therapeutic potential of targeting protein-RNA interactions has not been fully explored. While several approaches to block the between various RNA and protein partners have developed, rational efforts target pre-assembled complexes broadly pursued. This is despite recent commercial success risdiplam, high-resolution structure EIF4A-polypurine-Rocaglamide A ternary complex, which elucidates how compounds may recognize these pockets. These prominent examples indicate viability this approach, but important questions remain. For example, abundant are pockets in other complexes? Do such properties suitable for small molecule recognition? broad analysis 160 previously published RNP confirmed that interfacial RNA-protein both favorable would make them good candidates screening campaigns. conclusions expected implications especially those working on developing molecules bind directly structural elements.

Language: Английский

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Alternative Splicing in the Heart: The Therapeutic Potential of Regulating the Regulators

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13023 - 13023

Published: Dec. 4, 2024

Alternative splicing allows a single gene to produce variety of protein isoforms. Changes in isoform usage characterize virtually every stage the differentiation process and define physiological differences between cardiomyocytes with different function, at stages development, pathological function. Recent identification cardiac factors provided insights into mechanisms underlying alternative revealed how these impact functional properties heart. Alterations sarcomeric genes, cell signaling proteins, ion channels have been associated development conditions such as cardiomyopathy arrhythmia. RBM20, RBM24, PTBP1, RBFOX, QKI play key roles pathology. A better understanding their regulation will yield healthy inform molecular therapeutics.

Language: Английский

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