Genes

12 pages, 7319 KB

Open AccessArticle

Novel ITGB6 Mutations Causing Amelogenesis Imperfecta

by Hyemin Yin, Soojin Jang, Hyuntae Kim, James P. Simmer, Jan C.-C. Hu and Jung-Wook Kim

Genes 2026, 17(4), 431; https://doi.org/10.3390/genes17040431 - 8 Apr 2026

Background/Objectives: Amelogenesis imperfecta (AI) is a heterogeneous group of rare hereditary conditions mainly affecting the quantity and/or quality of tooth enamel. Its phenotypic expression is diverse, as is the mutational spectrum of the AI-causing genes and mutations. Integrins are cell-surface receptors that mediate [...] Read more.

Background/Objectives: Amelogenesis imperfecta (AI) is a heterogeneous group of rare hereditary conditions mainly affecting the quantity and/or quality of tooth enamel. Its phenotypic expression is diverse, as is the mutational spectrum of the AI-causing genes and mutations. Integrins are cell-surface receptors that mediate adhesion between cells and between cells and the extracellular matrix. Among these, mutations in integrin αvβ6 have been shown to cause AI; however, phenotypic variation exists between the knockout mouse model and human cases, as well as among different human AI families. Methods: We recruited AI families and performed mutational analysis using whole exome sequencing. Results: We identified compound heterozygous ITGB6 mutations in two families. In Family 1, a paternally transmitted nonsense mutation (NM_000888.5: c.1060C>T, p.(Gln354*)) and a maternally transmitted missense mutation (NM_000888.5: c.2312A>G, p.(Asn771Ser)) were identified; in Family 2, a paternal missense mutation (NM_000888.5: c.1693T>C, p.(Cys565Arg)) and a maternal frameshift mutation (NM_000888.5: c.2091delC, p.(Asn698Metfs*13)) were identified, each causing AI in the respective proband. Both probands exhibited generalized hypoplastic and hypomineralized AI, but no other extraoral symptoms. Conclusions: This report will not only expand the known mutational spectrum of the ITGB6 gene but also provide evidence for the genotype–phenotype correlations, thereby improving our understanding of the functional role of ITGB6 during amelogenesis. Full article

(This article belongs to the Special Issue Genetic, Epigenetic and Environmental Factors in Dental Development and Pathologies: Genes, Interactions and Dental Development)

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15 pages, 2366 KB

Open AccessArticle

Characterization of the Complete Mitochondrial Genome of Castanopsis tibetana Hance: A Precious Timber Species

by Zi-Fei Wang, Zhi-Tong Xiao, Xiao-Long Jiang, Feng Song and Fei Liu

Genes 2026, 17(4), 430; https://doi.org/10.3390/genes17040430 - 7 Apr 2026

Abstract

Background/Objectives: Castanopsis tibetana Hance (C. tibetana) is a valuable timber species in southern China. Its chloroplast and nuclear genomes have been characterized, but its mitochondrial genome (mitogenome) remains unknown. This study assembles and characterizes the first complete mitogenome of C. tibetana [...] Read more.

Background/Objectives: Castanopsis tibetana Hance (C. tibetana) is a valuable timber species in southern China. Its chloroplast and nuclear genomes have been characterized, but its mitochondrial genome (mitogenome) remains unknown. This study assembles and characterizes the first complete mitogenome of C. tibetana, elucidating its structural and evolutionary features. Methods: A hybrid approach combining Oxford Nanopore long reads and Illumina short reads was used. The mitogenome was assembled via iterative seed-based mapping and annotated via GeSeq and tRNAscan-SE. Repeats were identified via MISA, TRF, and REPuter. The RNA editing sites were predicted with the PREP suite. Phylogenetic analysis was performed on 14 conserved protein-coding genes from 13 species via maximum likelihood and Bayesian inference. Results: The mitogenome is a 554,078 bp circular molecule (GC 45.27%) encoding 51 genes (32 PCGs, 16 tRNAs, 3 rRNAs). It contains 202 simple sequence repeats (37.1% tetrameric). We predicted 53 C-to-U RNA editing sites, most frequently in nad7 and nad5. Codon usage showed bias, with 28 codons having RSCU > 1. Twenty fragments (6001 bp, 1.08% of the mitogenome) were transferred from the chloroplast. Phylogenomic analysis placed C. tibetana within Fagaceae, close to other Castanopsis species. Conclusions: This study provides the first comprehensive characterization of the C. tibetana mitogenome, revealing its structural architecture, repetitive landscape, RNA editing profile, and phylogenetic placement. These findings offer valuable genomic resources for understanding mitogenome evolution in Fagaceae and support future research on the conservation genetics and molecular breeding of this important tree species. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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9 pages, 1047 KB

Open AccessCase Report

The First Case of Kleefstra Syndrome in a Rwandan Patient with Global Developmental Delay

by Norbert Dukuze, Janvier Hitayezu, Jeanne Primitive Uyisenga, Esther Uwibambe, Jean Hubert Caberg, Vinciane Dideberg, Vincent Bours, Abdullateef Isiaka Alagbonsi, Leon Mutesa and Annette Uwineza

Genes 2026, 17(4), 429; https://doi.org/10.3390/genes17040429 - 7 Apr 2026

Abstract

Background: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of EHMT1; it is characterized by global developmental delay, intellectual disability, hypotonia, distinctive facial features, and variable congenital anomalies. Autistic features, behavioral abnormalities and severe speech impairment are frequently reported. [...] Read more.

Background: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of EHMT1; it is characterized by global developmental delay, intellectual disability, hypotonia, distinctive facial features, and variable congenital anomalies. Autistic features, behavioral abnormalities and severe speech impairment are frequently reported. However, molecularly confirmed cases of KS from Africa remain extremely limited, largely due to restricted access to genomic diagnostic infrastructures. Methods: We describe a 15-month-old patient from Rwanda presenting with neonatal hypotonia, global developmental delay, short stature, and characteristic dysmorphic facial features. Comprehensive clinical evaluation was performed, followed by trio-based exome sequencing to identify the underlying genetic cause of this neurodevelopmental disorder. Results: Exome sequencing identified a de novo heterozygous frameshift variant in EHMT1 (NM_024757.5: c.2871dup; p. Phe958Leufs*219), confirming the diagnosis of KS. Conclusions: This report presents the first molecularly confirmed case of KS in Rwanda. It highlights additional clinical features like bilateral 5th toe clinodactyly, short stature and absence of obesity in KS. There is a need to further delineate the study of EHMT1 and investigate the natural history of KS across different populations for optimal patient management and to reduce diagnostic odyssey. The diagnostic utility of exome sequencing for neurodevelopmental disorders needs to be strengthened, with strong emphasis on expanding genomic medicine to help diagnose rare diseases in resource-limited settings. Full article

(This article belongs to the Special Issue Genes and Pediatrics)

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16 pages, 3356 KB

Open AccessArticle

Molecular Characterization and In Vitro Functional Analysis of a 1-Cys Peroxiredoxin 6 from the Whiteleg Shrimp Penaeus vannamei

by Gunasekara Chathura Wikumpriya, W. S. P. Madhuranga and Chan-Hee Kim

Genes 2026, 17(4), 428; https://doi.org/10.3390/genes17040428 - 6 Apr 2026

Abstract

Background/Objectives: Peroxiredoxins (Prxs) are key antioxidant enzymes involved in cellular redox homeostasis. Prx6 is a multifunctional member of the Prx family that has been reported in other organisms to possess glutathione peroxidase and phospholipase A₂ (PLA₂)-related activities. However, the structural [...] Read more.

Background/Objectives: Peroxiredoxins (Prxs) are key antioxidant enzymes involved in cellular redox homeostasis. Prx6 is a multifunctional member of the Prx family that has been reported in other organisms to possess glutathione peroxidase and phospholipase A₂ (PLA₂)-related activities. However, the structural and immunological roles of 1-Cys Prx6 in crustaceans remain poorly understood. This study aimed to identify and characterize a Prx6 gene from Penaeus vannamei (PvPrx6) and to evaluate its potential involvement in antioxidant defense. Methods: PvPrx6 cDNA was identified and analyzed using bioinformatics and AlphaFold2 modeling. Tissue distribution and transcriptional responses to lipopolysaccharide (LPS), poly(I:C), and peptidoglycan (PGN) were examined by RT-qPCR. Recombinant PvPrx6 (rPvPrx6) was expressed in Escherichia coli, and its antioxidant activity was evaluated in vitro using a metal-catalyzed oxidation (MCO) assay. Results: PvPrx6 encodes a 219-amino-acid protein containing conserved AhpC/TSA and 1-Cys Prx domains. Sequence comparison and 3D modeling revealed conserved peroxidase (Thr⁴¹, Cys⁴⁴, Arg¹²⁷) and residues (His²³, Lys²⁹, Asp¹³⁵) corresponding to the reported PLA₂-associated motif. Structural analysis suggested that Lys²⁹ occupies a position corresponding to the Ser³² residue of human Prx6, although this did not imply functional equivalence. PvPrx6 transcripts were highly expressed in the lymphoid organ and hepatopancreas and were significantly induced at 12 h following immune challenge. rPvPrx6 exhibited dose-dependent protection against hydroxyl radical-mediated DNA damage under the experimental conditions. Conclusions: Collectively, these findings suggest that PvPrx6 retains conserved structural characteristics of Prx6 proteins and may contribute to antioxidant defense in P. vannamei. However, further studies are required to validate its enzymatic activity and in vivo functional roles. Full article

(This article belongs to the Special Issue Genetic Insights into Immunity and Pathogen Resistance)

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15 pages, 9861 KB

Open AccessArticle

Characterization of Chlorophyll Degradation Genes Reveals Gene Cluster HuSGR2 and HuSGR3 Promoting Chlorophyll Degradation in Pitaya Peel

by Wenting Wu, Tian Yang, Yun Lan, Zeyu Zheng, Xiaoying Ye, Meibing Ma, Canbin Chen and Fangfang Xie

Genes 2026, 17(4), 427; https://doi.org/10.3390/genes17040427 - 5 Apr 2026

Abstract

Background: Chlorophyll degradation is a characteristic sign of fruit ripening. However, the chlorophyll degradation pathway during pitaya fruit development remains unexplored. Methods and Results: Here, chlorophyll contents showed a downward trend across the five developmental stages of ‘Jindu No.1’ pitaya peels. Based on [...] Read more.

Background: Chlorophyll degradation is a characteristic sign of fruit ripening. However, the chlorophyll degradation pathway during pitaya fruit development remains unexplored. Methods and Results: Here, chlorophyll contents showed a downward trend across the five developmental stages of ‘Jindu No.1’ pitaya peels. Based on the pitaya genome data, twenty chlorophyll degradation genes were identified, including two NYCs, three CLHs, five SGRs, six PAOs, and four RCCRs, spread across eight pitaya chromosomes. In addition, their phylogenetic relationships, conserved motifs, and domains were analyzed using homologous genes from beet and Arabidopsis species. Transcriptomic data and RT-qPCR analyses of these genes suggested that three HuSGRs demonstrated a significant upward trend during pitaya peel maturation. Indeed, the HuSGR1 has the complete gene structure, including the chloroplast transit peptide, SGR domain, and variable C-terminal region. However, HuSGR2 and HuSGR3 contained the N- and C-terminal sequences, respectively, of HuSGR1. They were separated by a 690 bp distance on chromosome 8, forming a gene cluster. Overexpressed HuSGR2 or HuSGR3 alone resulted in a significant decrease in chlorophyll contents in tobacco leaves. Notably, a more obvious reduction of chlorophyll contents was observed when overexpressing them together. Conclusions: Our results show that HuSGR2 and HuSGR3 were involved in accelerating the chlorophyll degradation process, providing new insights into the molecular basis of color formation in pitaya peels. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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14 pages, 1429 KB

Open AccessArticle

Genome-Wide Identification and Expression Profiling of the PYL Gene Family in Watermelon Under Abiotic Stresses

by Guangpu Lan, Yidong Guo, Jun Hu, Jincan Huang, Ziye Pan, Yingda Chen, Xian Zhang, Zhongyuan Wang, Yongchao Yang and Chunhua Wei

Genes 2026, 17(4), 426; https://doi.org/10.3390/genes17040426 - 4 Apr 2026

Abstract

Background: PYR/PYL/RCAR proteins are core abscisic acid (ABA) receptors that play essential roles in ABA signal transduction, plant growth and development, and abiotic stress responses. However, the PYL gene family in watermelon (Citrullus lanatus) has not been systematically characterized, limiting our [...] Read more.

Background: PYR/PYL/RCAR proteins are core abscisic acid (ABA) receptors that play essential roles in ABA signal transduction, plant growth and development, and abiotic stress responses. However, the PYL gene family in watermelon (Citrullus lanatus) has not been systematically characterized, limiting our understanding of ABA-mediated stress adaptation in this economically important crop. Methods: A genome-wide analysis was performed to identify ClPYL genes in watermelon using a hidden Markov model search. Phylogenetic relationships were reconstructed using the maximum likelihood method. Segmental duplication events were analyzed using synteny analysis. Conserved motifs, gene structures, and promoter cis-acting elements were characterized using MEME and PlantCARE. Expression profiles under drought, salt, and cold stresses were examined by quantitative real-time PCR (qRT-PCR) with three biological replicates. Results: In this study, 15 ClPYL genes were identified in watermelon through genome-wide analysis. Phylogenetic reconstruction classified these genes into four subfamilies, with subfamily II being exclusively present in cucurbits—a lineage-specific feature not observed in Arabidopsis. Synteny analysis revealed eight segmental duplication events involving members of subfamilies I, III, and IV, while subfamily II members were not associated with these duplications. Members within the same subfamily share similar exon-intron structures and conserved motifs. Promoter analysis revealed that ClPYL genes are enriched with various cis-acting elements associated with hormone signaling and abiotic stress responses. Expression profiling demonstrated that ClPYL genes exhibit diverse and dynamic expression patterns under drought, high-salinity, and cold stresses. Notably, genes such as ClPYL5 under drought, ClPYL02 under salt, and ClPYL15 under cold stress displayed persistent stress-responsive expression. Conclusions: These findings reveal the evolutionary conservation and diversification of the PYL family in watermelon and provide a set of candidate genes for functional studies aimed at dissecting ABA-mediated stress adaptation. This work establishes a genomic framework for developing stress-resilient watermelon varieties through molecular breeding. Full article

(This article belongs to the Topic Vegetable Breeding, Genetics and Genomics, 2nd Volume)

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17 pages, 2605 KB

Open AccessArticle

Detecting the Pre-Disease State of Single Sample Through the Change in Local Network Enrichment Level

by Zhenshen Bao, Ying Wang, Zhiyu Liu, Xianbin Li and Yunfei Bai

Genes 2026, 17(4), 425; https://doi.org/10.3390/genes17040425 - 3 Apr 2026

Abstract

Background: In complex biological processes, there exists a tipping point (pre-disease state) when the system undergoes a sudden and dramatic shift to a contrasting state. Accurate detection of the pre-disease state is critical for preventive medicine. However, precise detection of the pre-disease [...] Read more.

Background: In complex biological processes, there exists a tipping point (pre-disease state) when the system undergoes a sudden and dramatic shift to a contrasting state. Accurate detection of the pre-disease state is critical for preventive medicine. However, precise detection of the pre-disease state proves challenging due to the clinical single-sample problem. Methods: To address this challenge, in this study, we introduce a novel single-sample pre-disease state detection method based on the change in local network enrichment level. Results: We validated the proposed method on five independent real datasets, including one influenza virus infection time-course dataset and four tumor datasets. Experimental results confirmed that the proposed method can accurately identify the pre-disease state prior to overt disease onset. Further analysis verified key genes identified by the proposed method in pre-disease state are associated with viral infection and immune dysregulation for the influenza dataset, and tumor metastasis for the tumor datasets. Conclusions: These results demonstrate that this method is a robust and biologically interpretable tool for single-sample pre-disease state detection, with great potential for clinical translation in individualized preventive medicine. Full article

(This article belongs to the Section Bioinformatics)

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14 pages, 7172 KB

Open AccessArticle

Identification of Three Novel MAGED2 Variants Causing Antenatal Bartter Syndrome in Three Chinese Families

by Shufa Yang, Xiaojuan Li, Haili Jiang, Jiahui Cheng, Changlong Li, Xinyi Xie and Xiaoqin Xiao

Genes 2026, 17(4), 424; https://doi.org/10.3390/genes17040424 - 3 Apr 2026

Abstract

Background/Objectives: We aimed to report three novel MAGED2 variants associated with transient antenatal Bartter syndrome (TABS) and to summarize the prenatal and postnatal features of MAGED2-related TABS through case analysis and literature review. Methods: Three unrelated Chinese families with polyhydramnios-affected [...] Read more.

Background/Objectives: We aimed to report three novel MAGED2 variants associated with transient antenatal Bartter syndrome (TABS) and to summarize the prenatal and postnatal features of MAGED2-related TABS through case analysis and literature review. Methods: Three unrelated Chinese families with polyhydramnios-affected pregnancies underwent genetic testing. Clinical data, including prenatal imaging, delivery details, and postnatal outcomes were reviewed. A literature review of reported MAGED2 variants and associated phenotypes was conducted. Results: Three previously unreported MAGED2 variants were identified: two frameshift variants (c.1511del [p.Gly504Alafs*72] and c.338del [p.Pro113ArgfsTer4]) and one deletion (chrX:54,820,664–54,839,053 [GRCh37]). All fetuses presented with polyhydramnios; two were large for gestational age (LGA). Additional findings included ventriculomegaly and scrotal enlargement. Two male infants were delivered at 33 weeks following repeated amnioreduction, with transient postnatal electrolyte abnormalities and normal neurodevelopment at 3 and 4 years. One fetus with a frameshift variant died in utero at 26 + 1 weeks. A literature review of 53 cases revealed 38 distinct MAGED2 variants, predominantly null variants (65.8%). Polyhydramnios was the most consistent antenatal sign. No intellectual disability was reported in surviving individuals. Conclusions: These findings expand the MAGED2 mutational spectrum. Polyhydramnios and LGA represents the most frequent features in TABS. In fetuses presenting with early-onset severe polyhydramnios (around 19–20 weeks of gestation), particular attention should be paid to possible exon-level or partial deletions involving MAGED2 during genetic evaluation. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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12 pages, 453 KB

Open AccessReview

A Mini Narrative Review on Human DNA Transfer Involving Dogs and Cats and Their Role in Forensic Investigation

by Carla Bini, Alessia Trasatti, Arianna Giorgetti, Sara Amurri, Giulia Fazio and Susi Pelotti

Genes 2026, 17(4), 423; https://doi.org/10.3390/genes17040423 - 2 Apr 2026

Abstract

Background/Objectives: The potential role of domestic animals in DNA transfer, persistence, prevalence and recovery (TPPR) warrants careful consideration in forensic contexts. This mini narrative review aims to provide an updated overview of human DNA transfer involving household dogs and cats as vectors, to [...] Read more.

Background/Objectives: The potential role of domestic animals in DNA transfer, persistence, prevalence and recovery (TPPR) warrants careful consideration in forensic contexts. This mini narrative review aims to provide an updated overview of human DNA transfer involving household dogs and cats as vectors, to clarify their forensic relevance, and to identify key considerations for the design of future experimental research. Methods: A narrative review was conducted using multiple electronic databases as search engines without restriction related to the timing of publication. Results: Experimental evidence shows that dogs and cats readily acquire human DNA following even brief contact, acting as reservoirs for primary DNA transfer. Once acquired, human DNA can be redistributed via secondary transfer to a wide range of substrates, such as gloved hands, vehicle interiors, clothing, and surfaces. Moreover, multi-step and higher-order transfer events have been documented, highlighting the complexity of DNA transfer involving household animals. Conclusions: The sampling on pets may be included in certain scenarios and may contribute to building a Bayesian network together with the experimental data. To deal with uncertainty during probability assignment, more experimental data, especially addressing the main variables impacting DNA TPPR involving pets, should be generated and are highly needed to assist in activity level evaluation. Full article

(This article belongs to the Special Issue Advanced Research in Forensic Genetics)

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17 pages, 661 KB

Open AccessCommunication

Population Genetic Data for 23 STR Loci of the Pech Ethnic Group in Honduras

by Antonieta Zuniga, Yolly Molina, Karen Amaya, Zintia Moya, Patricia Soriano, Digna Pineda, Yessica Pinto, Oscar García and Isaac Zablah

Genes 2026, 17(4), 422; https://doi.org/10.3390/genes17040422 - 1 Apr 2026

Abstract

Background: The Pech ethnic group, comprising approximately 6024 individuals in northeastern Honduras, represents one of the country’s smallest indigenous communities with a rich cultural heritage extending to pre-Columbian times. Despite their historical significance, no population genetic studies have been conducted on this [...] Read more.

Background: The Pech ethnic group, comprising approximately 6024 individuals in northeastern Honduras, represents one of the country’s smallest indigenous communities with a rich cultural heritage extending to pre-Columbian times. Despite their historical significance, no population genetic studies have been conducted on this group, and population-specific databases are essential for accurate forensic applications. Methods: Allele frequencies for 23 autosomal short tandem repeat (STR) loci were determined in 100 unrelated Pech individuals (58 females, 42 males) from communities in the departments of Olancho, Colón, and Gracias a Dios. DNA was extracted from blood samples collected on FTA cards and amplified using the PowerPlex Fusion 6C System. Statistical parameters were calculated using Genepop v4.2 and Arlequin v5.3.2.2. Results: All loci exhibited substantial polymorphism. No statistically significant deviations from Hardy–Weinberg equilibrium were detected after Bonferroni correction (α = 0.0022). Expected heterozygosity ranged from 0.4033 (TH01) to 0.8563 (FGA). The combined power of discrimination exceeded 99.9999%, and the combined chance of exclusion was 99.9999%. Conclusions: This study presents the first genetic characterization of the Pech population, providing essential reference data for forensic identification, paternity testing, and population genetics research. The dataset fills a critical gap in the Honduran forensic genetic infrastructure and contributes to understanding indigenous Central American genetic diversity, enabling accurate forensic analyses for individuals of Pech ancestry in compliance with CODIS and ESS standards. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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13 pages, 774 KB

Open AccessArticle

NLRP12 as a Regulator of Inflammation: Insights into the Correlation with Autoinflammatory Disorders

by Beatrice Rosa, Elisabetta Tabolacci, Roberta Pietrobono, Eugenio Sangiorgi, Fiorella Gurrieri, Pietro Chiurazzi, Ludovico Luca Sicignano, Elena Verrecchia, Maurizio Genuardi, Donato Rigante and Raffaele Manna

Genes 2026, 17(4), 421; https://doi.org/10.3390/genes17040421 - 1 Apr 2026

Abstract

Background: Dysregulation of the innate immune system is a key feature of autoinflammatory disorders, characterized by recurrent or chronic inflammation in the absence of high-titer autoantibodies and antigen-specific T cells. Among regulators of innate immunity, NLRP12 has emerged as an important modulator [...] Read more.

Background: Dysregulation of the innate immune system is a key feature of autoinflammatory disorders, characterized by recurrent or chronic inflammation in the absence of high-titer autoantibodies and antigen-specific T cells. Among regulators of innate immunity, NLRP12 has emerged as an important modulator of inflammatory signaling pathways. As a member of the nucleotide-binding oligomerization domain-like receptor (NLR) family, NLRP12 negatively regulates nuclear factor (NF)-κB activity and contributes to immune homeostasis. However, the clinical significance of NLRP12 variants and their association with disease phenotypes remain incompletely understood. This study aims to summarize current knowledge on the molecular role of NLRP12 and its involvement in autoinflammatory manifestations. Methods: A narrative review of the literature on NLRP12’s molecular functions and role in autoinflammatory diseases was performed. In addition, a cohort of 20 patients with recurrent fevers carrying NLRP12 variants was analyzed from a clinical perspective, evaluating genetic findings and clinical features. Results: Available evidence indicates that NLRP12 regulates inflammatory signaling, particularly through modulation of NF-κB activity. Variants in the NLRP12 gene have been associated with a spectrum of autoinflammatory phenotypes, ranging from periodic fever syndromes to broader systemic inflammatory manifestations. Clinical evaluation of the cohort confirmed the heterogeneity of disease presentations among individuals carrying NLRP12 variants. Conclusions: NLRP12 plays an important role in the regulation of innate immune responses and may contribute to autoinflammatory phenotypes. Integrating molecular data with clinical observations may improve the understanding of NLRP12 variants and support more accurate diagnostic and therapeutic strategies. Full article

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24 pages, 321 KB

Open AccessReview

The Effect of Wildfire Exposure: Neurological Outcomes, Mental Health, and Epigenetic Insights

by Haneen Abou El Khair, Venika Toor and Lei Cao-Lei

Genes 2026, 17(4), 420; https://doi.org/10.3390/genes17040420 - 1 Apr 2026

Abstract

Background/Objectives: Wildfires are increasing in frequency and intensity worldwide, leading to widespread exposure to wildfire smoke and associated environmental stressors. While the respiratory and cardiovascular effects of wildfire smoke are well established, the potential neurological and mental health consequences have received growing [...] Read more.

Background/Objectives: Wildfires are increasing in frequency and intensity worldwide, leading to widespread exposure to wildfire smoke and associated environmental stressors. While the respiratory and cardiovascular effects of wildfire smoke are well established, the potential neurological and mental health consequences have received growing attention. This narrative review synthesizes evidence from animal and human studies examining the effects of wildfire exposure on neurological function, behavior, and mental health, and explores the potential role of epigenetic mechanisms. Methods: A structured literature search was conducted using PubMed to identify original research articles examining wildfire exposure in relation to neurological, behavioral, mental health, or epigenetic outcomes. Both human and animal studies were included. Results: Experimental animal studies suggest that wildfire smoke exposure can induce neuroinflammation, blood–brain barrier disruption, metabolic alterations, and behavioral changes. Human studies conducted in wildfire-affected populations frequently report an elevated prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), and sleep disturbances. However, many of these studies reflect mental health outcomes associated with wildfire disaster exposure, including evacuation and psychosocial stress, whereas only a subset of studies quantify wildfire smoke or PM_2.5 exposure. Emerging evidence from both animal models and human studies indicates that wildfire exposure may be associated with changes in epigenetic regulation, including alterations in DNA methylation and miRNA expression. Conclusions: Current evidence suggests that wildfire exposure may influence neurological and mental health outcomes through biological and psychosocial pathways. However, the literature remains heterogeneous, and the independent effects of wildfire smoke exposure are often difficult to disentangle from disaster-related stressors. In addition, human evidence linking wildfire exposure to epigenetic changes remains limited, restricting causal inference. Further longitudinal and mechanistic studies integrating exposure assessment, neurological outcomes, and molecular profiling are needed to clarify these relationships. Full article

(This article belongs to the Special Issue Epigenetic Insights into Stress-Related Disorders)

28 pages, 1720 KB

Open AccessReview

Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA

by Ayse Yesbek Kaymaz, Gamze Bora-Akoğlu, Hayat Erdem Yurter and Christopher Grunseich

Genes 2026, 17(4), 419; https://doi.org/10.3390/genes17040419 - 1 Apr 2026

Abstract

Advances in technology have provided a better understanding of the genetic basis of neurodegenerative disorders and their underlying molecular pathophysiology. However, treating these disorders with conventional strategies is a major challenge. The approval of gene targeted therapy for spinal muscular atrophy (SMA) has [...] Read more.

Advances in technology have provided a better understanding of the genetic basis of neurodegenerative disorders and their underlying molecular pathophysiology. However, treating these disorders with conventional strategies is a major challenge. The approval of gene targeted therapy for spinal muscular atrophy (SMA) has laid the foundation for developing highly personalized therapies for other neurodegenerative disorders. As intensive research and efforts to advance gene targeted therapies continue, this review provides an overview of viral and non-viral vectors and delivery methods, as well as treatment strategies, including gene addition, replacement, editing, silencing, and splice modulation. Gene targeted approaches and clinical trials for SMA and amyotrophic lateral sclerosis (ALS) have demonstrated success, and additional studies are in progress. The design of efficient clinical trials which facilitate successful translation into clinical practice is of critical importance. Key considerations include the selection of appropriate disease models, understanding the natural history of the disease, and establishing well-defined outcome measures to assess prognosis of the disease and therapeutic efficacy. Finally, the precision of CRISPR-based gene editing offers the potential for one-time corrective therapies for monogenic disorders like SMA and SOD1-ALS. Full article

(This article belongs to the Special Issue Genetics and Treatment of Inherited Neurological Diseases of the Spinal Cord)

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10 pages, 633 KB

Open AccessArticle

Genotoxicity Assessment in Occupational Health Personnel Exposed to Cytostatic Drugs in a Peruvian Hospital

by Luis Miguel Serquén López, Greta Milagros Mendoza Cornejo, Viviana Brigith Torres Merino, Blanca Pacheco Gonzales, Herry Lloclla Gonzales and Ricardo Leonidas de Jesús Vélez Chicoma

Genes 2026, 17(4), 418; https://doi.org/10.3390/genes17040418 - 31 Mar 2026

Abstract

The use of cytostatic drugs for cancer treatment is currently the main weapon in the fight against cancer; however, prolonged exposure of healthcare personnel can cause adverse toxic effects. Objective: To determine the genotoxicity caused by exposure to cytostatic drugs, using the comet [...] Read more.

The use of cytostatic drugs for cancer treatment is currently the main weapon in the fight against cancer; however, prolonged exposure of healthcare personnel can cause adverse toxic effects. Objective: To determine the genotoxicity caused by exposure to cytostatic drugs, using the comet assay, in workers in the oncology department of a tertiary hospital in northern Peru. Methodology: Descriptive, quantitative, correlational, and cross-sectional study. The population consisted of two groups of workers: exposed (n = 40) and unexposed (n = 40). The alkaline lysis comet DNA technique was used on peripheral blood cells; tailing moment and tailing percentage indicators were evaluated. Results: Using nonparametric tests, the percentage and tail moment showed no significant differences, with p values of 0.8928 and 0.4675, respectively. The distribution observed in the group exposed to cytostatic drugs (pharmacists and pharmacy technicians) compared to the control group showed a normal distribution, with a tail moment of 8.29 vs. 3.03 and a percentage of tail of 37.12 vs. 23.24, respectively. Multivariate analysis showed that the tail moment variable was 11.56% greater in the group of pharmacists and pharmacy technicians (p = 0.0119) compared to the other participants. Conclusions: Although no significant difference was found, a trend toward a higher percentage and tail moment was observed in the group exposed to cytostatic drugs. Furthermore, the group of pharmacists and pharmacy technicians, compared to the other professions, showed significantly greater damage. Full article

(This article belongs to the Section Toxicogenomics)

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9 pages, 1018 KB

Open AccessArticle

Buffy Coat Enrichment Improves the Success Rate of Conventional Cytogenetics in Hypocellular Specimens: A Prospective Quality Improvement Study

by Gokce A. Toruner, Nawal Imtiaz, Andrew M. McCoy, Melissa Robinson, Griselda J. Cardona, Sarita S. Delgado, Su Yang, Qing Wei, L. Jeffrey Medeiros and Guilin Tang

Genes 2026, 17(4), 417; https://doi.org/10.3390/genes17040417 - 31 Mar 2026

Abstract

Background: Specimens with low cell counts may fail to yield sufficient analyzable metaphases or are rejected for chromosomal analysis. Buffy coat enrichment (BCE) concentrates nucleated cells prior to culture; however, its impact on routine cancer cytogenetics has not been systematically evaluated. Methods [...] Read more.

Background: Specimens with low cell counts may fail to yield sufficient analyzable metaphases or are rejected for chromosomal analysis. Buffy coat enrichment (BCE) concentrates nucleated cells prior to culture; however, its impact on routine cancer cytogenetics has not been systematically evaluated. Methods: We first validated BCE in hypocellular specimens (<5 K/µL) and then conducted a prospective quality improvement study from November 2024 to October 2025, encompassing 12,088 specimens. A phased intervention strategy was implemented by performing BCE on specimens with cell counts of 2.0–4.9 K/µL (designated as phase I); followed by expanding BCE to specimens with cell counts of 1.0–4.9 K/µL (phase II). Outcomes were assessed by the rate of successful karyotypes, defined as ≥10 analyzable metaphases. Results: In the validation cohort (cell counts < 5 K/µL), BCE improved the success rate across all cell count strata. In the prospective study cohort, implementation of BCE increased the overall success rate from 78% at baseline to 83% in phase I, and further increased to 90% in phase II. Conclusions: BCE significantly improves the success rate of chromosomal analysis by increasing the yield of metaphases in hypocellular specimens. This simple and scalable intervention reduces specimen rejection and enhances diagnostic yield in routine cancer cytogenetics. Full article

(This article belongs to the Section Cytogenomics)

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21 pages, 1930 KB

Open AccessArticle

Can Cell-Free DNA in the Culture Medium Predict the Chromosomal Constitution of Preimplantation Embryos? Final Results from a Multicenter Study with 2539 Blastocysts

by Luis Navarro-Sánchez, Denny Sakkas, Nilo Frantz, Emilio de la Fuente Lucena, William Venier, Daria Maria Soscia, Gerardo Barroso, Claudio Bisioli, Michael DiMattina, Bilgen Teke, Luis Ernesto Escudero and Carmen Rubio

Genes 2026, 17(4), 416; https://doi.org/10.3390/genes17040416 - 31 Mar 2026

Abstract

Background/Objectives: In the last decade, non-invasive methods for aneuploidy detection have been explored. The most successful approach involves analyzing the cell-free DNA (cfDNA) released by the embryo into the culture medium. The main objective of this study is to examine the technical feasibility [...] Read more.

Background/Objectives: In the last decade, non-invasive methods for aneuploidy detection have been explored. The most successful approach involves analyzing the cell-free DNA (cfDNA) released by the embryo into the culture medium. The main objective of this study is to examine the technical feasibility of this new approach called non-invasive PGT-A or niPGT-A. In addition, as an exploratory objective, the impact of the niPGT-A results on clinic outcomes will be assessed. Methods: This was a multicenter, international study that included 716 patients and 2539 blastocysts (ClinicalTrials.gov: NCT03520933). Each embryo was cultured following a specific protocol for niPGT-A. Individual spent blastocyst medium (SBM) and trophectoderm (TE) biopsy were obtained, analyzed, and compared to assess concordance. In a subset of embryos, the comparison also included an inner cell mass (ICM) biopsy. Clinical outcomes from the embryo transfers performed (all based on the TE result) were registered, and results were analyzed blindly regarding the impact of aneuploidies in the culture medium. Results: The concordance rate between SBM and TE was 79.1% (range: 74.1–82.1; cycles with autologous oocytes). This value increased to 87.0% when comparing SBM and ICM. Applying an adapted embryo culture protocol to collect the SBM for niPGT-A did not affect blastocyst quality. Analysis of the embryo transfers performed (n = 265) revealed a trend towards lower miscarriage rate in blastocysts where both TE and SBM were concordant and euploid (13.0%), compared to blastocysts with a euploid TE and an aneuploid SBM (22.2%). Conclusions: The results obtained show a high concordance between the SBM and TE biopsies. Although additional refinement of the technique would further increase niPGT-A’s performance, the results obtained support the potential use of this non-invasive approach for aneuploidy detection. The high concordance of the cfDNA present in the SBM with the corresponding ICM biopsy and the miscarriage rate observed in cases with an aneuploid SBM, despite the euploid TE results, also support niPGT-A’s capacity to assess embryo aneuploidies and its potential as a prioritization system for selecting blastocysts to transfer. This approach could hold special interest in patients with no PGT-A indications, couples that prefer not to biopsy their embryos or those who do not have access to invasive PGT-A. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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14 pages, 1718 KB

Open AccessArticle

Lineage-Specific Sex-Biased Transcriptional Programs in Healthy Human Truncal Skin Revealed by Single-Cell Transcriptomics

by Yu Yang, Honghao Yu and Binbin Lai

Genes 2026, 17(4), 415; https://doi.org/10.3390/genes17040415 - 31 Mar 2026

Abstract

Background/Objectives: Sex differences influence skin physiology, immune regulation, and disease susceptibility, but the cellular organization of sex-biased transcriptional programs in healthy human skin remains incompletely defined. We aimed to define sex-associated differences in cellular composition and gene expression in healthy adult truncal [...] Read more.

Background/Objectives: Sex differences influence skin physiology, immune regulation, and disease susceptibility, but the cellular organization of sex-biased transcriptional programs in healthy human skin remains incompletely defined. We aimed to define sex-associated differences in cellular composition and gene expression in healthy adult truncal skin at single-cell resolution. Methods: We constructed a sex-resolved single-cell transcriptomic atlas of healthy human truncal skin by integrating scRNA-seq data from 12 donors (5 males, 7 females). After quality control, 107,967 cells were classified into 14 major cell types. Sex-associated differences were assessed using donor-level pseudo-bulk analyses at both whole-skin and cell-type-resolved levels. Results: The cellular composition was conserved between sexes, with significant differences in mast cells and regulatory T cells. Whole-skin pseudo-bulk analysis identified distinct male-biased and female-biased transcriptional programs. Male-biased signals were linked to extracellular matrix organization and immune responses, while female-biased signals involved ion transport and neuromodulation. Cell-type-resolved analysis revealed that most sex-biased genes were lineage-specific, with minimal cross-lineage sharing. Conclusions: Sexual dimorphism in healthy human truncal skin is encoded through lineage-structured transcriptional regulation rather than broad compositional changes, providing a framework for understanding sex-biased skin homeostasis and disease susceptibility. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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19 pages, 2305 KB

Open AccessReview

Single-Cell Multi-Omics Reveal Gene Regulatory Mechanisms Underlying Cardiac Embryonic Development

by Enqi Feng, Xuejia Zheng, Feng Zhu, Liu Xiang, Chengcheng Liu, Leping Wang, Yanni Cao and Yong Dai

Genes 2026, 17(4), 414; https://doi.org/10.3390/genes17040414 - 31 Mar 2026

Abstract

Background/Objectives: Cardiac embryonic development is a highly coordinated and dynamic process governed by precise spatiotemporal gene regulation. Increasing evidence indicates that cellular heterogeneity and lineage specification during heart development are tightly controlled by complex gene regulatory networks (GRNs) and epigenetic mechanisms. Recent advances [...] Read more.

Background/Objectives: Cardiac embryonic development is a highly coordinated and dynamic process governed by precise spatiotemporal gene regulation. Increasing evidence indicates that cellular heterogeneity and lineage specification during heart development are tightly controlled by complex gene regulatory networks (GRNs) and epigenetic mechanisms. Recent advances in single-cell multi-omics technologies provide unprecedented resolution to dissect these regulatory processes. This review aims to summarise current applications of single-cell multi-omics approaches to elucidate gene regulatory mechanisms underlying cardiac embryogenesis and their implications for congenital heart disease (CHD). Methods: We systematically reviewed recent literature on single-cell RNA sequencing (scRNA-seq), single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), spatial transcriptomics, and integrative multi-omics analyses applied to embryonic heart development. Studies were analysed to evaluate how these technologies contribute to cell-type identification, lineage trajectory reconstruction, GRN inference, and epigenetic landscape characterisation. Results: Single-cell multi-omics approaches have enabled the construction of high-resolution cardiac cell atlases, revealing previously unrecognised cellular heterogeneity and transitional states during heart development. Integrative analyses of transcriptomic and chromatin accessibility data have provided insights into lineage commitment, key transcription factors, enhancer–promoter interactions, and dynamic GRNs. These findings have advanced understanding of developmental genetics in cardiac morphogenesis and offered new perspectives on the molecular mechanisms underlying CHD. Conclusions: Single-cell multi-omics technologies provide a powerful framework for investigating gene regulatory mechanisms during cardiac embryogenesis. Continued methodological refinement and integrative analyses are expected to further clarify developmental processes and facilitate translational insights into CHD. Full article

(This article belongs to the Section Bioinformatics)

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31 pages, 1676 KB

Open AccessSystematic Review

Phenotypic Diversity in Maize Landraces: A Systematic Review of Global Patterns, Methodological Approaches, and Implications for Breeding

by Suwilanji Nanyangwe, Arsenio Daniel Ndeve, Pedro Fato, Paulino Munisse, Kolawole Peter Oladiran, Constantino Francisco Lhamine and Mable Chebichii Kipkoech

Genes 2026, 17(4), 413; https://doi.org/10.3390/genes17040413 - 31 Mar 2026

Abstract

Background/Objective: Maize (Zea mays L.) is a globally important cereal crop widely cultivated for food, feed, fodder, biofuel production, and various industrial applications. Maize landraces represent a valuable source of genetic diversity that supports adaptationand resilience across diverse agroecological environments. However, evidence [...] Read more.

Background/Objective: Maize (Zea mays L.) is a globally important cereal crop widely cultivated for food, feed, fodder, biofuel production, and various industrial applications. Maize landraces represent a valuable source of genetic diversity that supports adaptationand resilience across diverse agroecological environments. However, evidence on phenotypic diversity based on agro-morphological traits in these landraces remains fragmented across regions and varying analytical approaches. This review synthesized global evidence on phenotypic variation, heritability patterns, experimental designs, statistical methods, and the extent of integration between phenotypic and molecular data. Methods: A systematic literature search was conducted in GoogleScholar, ScienceDirect, PubMed and AGRIS for studies published between 2000 and 2025 evaluating phenotypic diversity in maize landraces. The review followed PRISMA 2020 guidelines, and f50 studies from 30 countries met the eligibility criteria. Results: Substantial and structured phenotypic diversity was consistently reported across studies, with flowering time, plant architecture, and ear and kernel traits emerging as major contributors to landrace differentiation. Traits with moderate to high heritability were mainly morphological and phenological, suggesting relative genetic control and potential suitability for phenotypic selection. In contrast, grain yield showed greater environmental sensitivity and variable heritability, reflecting complex inheritance and genotype × environment interactions. Although molecular markers were incorporated in a some studies, integrative analyses linking phenotypic and genetic data remained limited. Conclusions: Phenotypic evaluation remains a reliable approach for characterizing maize landrace diversity. However, standardized methodologies, greater integration with molecular data and cross-environment validation are needed to strengthen inference and utilization in breeding and conservation. The review also provides recommendations for improving agro-morphological assessment in maize landraces. Full article

(This article belongs to the Special Issue Genetic and Morphological Diversity in Plants)

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