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Article ; Online: Prenatal identification of a pathogenic maternal

Graziani, Ludovico / Nuovo, Sara / Pisaneschi, Elisa / Carriero, Miriam Lucia / Baghernajad Salehi, Leila / Nardone, Anna Maria / Manganaro, Lucia / Novelli, Antonio / D'Apice, Maria Rosaria / Mappa, Ilenia / Novelli, Giuseppe

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2024 Volume 37, Issue 1, Page(s) 2344718

Abstract: Objective: Holoprosencephaly (HPE) is the most common aberration of forebrain development, and it leads to a wide spectrum of developmental and craniofacial anomalies. HPE etiology is highly heterogeneous and includes both chromosomal abnormalities and ... ...

Abstract	Objective: Holoprosencephaly (HPE) is the most common aberration of forebrain development, and it leads to a wide spectrum of developmental and craniofacial anomalies. HPE etiology is highly heterogeneous and includes both chromosomal abnormalities and single-gene defects. Methods: Here, we report an Results: Individuals with germline pathogenic variants in Conclusion: The presented case supports the role of exome sequencing in prenatal diagnosis when fetal midline structural anomalies are suggestive of a genetic etiology, as early as the first trimester of gestation. The profound heterogeneity of
MeSH term(s)	Humans ; Female ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; Pregnancy ; Holoprosencephaly/genetics ; Holoprosencephaly/diagnosis ; Adult ; Prenatal Diagnosis/methods ; Exome Sequencing ; Ultrasonography, Prenatal ; Prosencephalon/abnormalities ; Prosencephalon/embryology ; Heterozygote
Chemical Substances	Receptor, Fibroblast Growth Factor, Type 1 (EC 2.7.10.1) ; FGFR1 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2024-04-28
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2024.2344718
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Article ; Online: PCSK3

Latini, Andrea / De Benedittis, Giada / Colafrancesco, Serena / Perricone, Carlo / Novelli, Giuseppe / Novelli, Lucia / Priori, Roberta / Ciccacci, Cinzia / Borgiani, Paola

Genes

2023 Volume 14, Issue 5

Abstract: Background: The : Methods: We investigated the : Results: We observed, by RT-qPCR, that the : Conclusions: Our data suggest that Furin could play a role in SS development, also promoting IFN-γ secretion. ...

Abstract	Background: The Methods: We investigated the Results: We observed, by RT-qPCR, that the Conclusions: Our data suggest that Furin could play a role in SS development, also promoting IFN-γ secretion.
MeSH term(s)	Humans ; Furin/genetics ; Gene Expression ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Leukocytes, Mononuclear/metabolism ; Promoter Regions, Genetic ; Sjogren's Syndrome
Chemical Substances	Furin (EC 3.4.21.75) ; Interferon-gamma (82115-62-6) ; FURIN protein, human (EC 3.4.21.75)
Language	English
Publishing date	2023-04-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14050981
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Article ; Online: Pain in axial spondyloarthritis: role of the JAK/STAT pathway.

Selmi, Carlo / Chimenti, Maria Sole / Novelli, Lucia / Parikh, Bhumik K / Morello, Francesca / de Vlam, Kurt / Ciccia, Francesco

Frontiers in immunology

2024 Volume 15, Page(s) 1341981

Abstract: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options ... ...

Abstract	Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.
MeSH term(s)	Humans ; Janus Kinases/metabolism ; Signal Transduction ; Janus Kinase Inhibitors/therapeutic use ; STAT Transcription Factors/metabolism ; Pain ; Axial Spondyloarthritis
Chemical Substances	Janus Kinases (EC 2.7.10.2) ; Janus Kinase Inhibitors ; STAT Transcription Factors
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1341981
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Article ; Online: Co-Inheritance of Pathogenic Variants in

Graziani, Ludovico / Zampatti, Stefania / Carriero, Miriam Lucia / Minotti, Chiara / Peconi, Cristina / Bengala, Mario / Giardina, Emiliano / Novelli, Giuseppe

Genes

2023 Volume 14, Issue 8

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, and it is typically caused ... ...

Abstract	Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, and it is typically caused by
MeSH term(s)	Humans ; Polycystic Kidney, Autosomal Dominant/genetics ; Genes, Regulator ; Polycystic Kidney Diseases ; Siblings ; Alleles
Language	English
Publishing date	2023-08-06
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14081589
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Article ; Online: Emerging Role of microRNAs and Long Non-Coding RNAs in Sjögren's Syndrome.

De Benedittis, Giada / Ciccacci, Cinzia / Latini, Andrea / Novelli, Lucia / Novelli, Giuseppe / Borgiani, Paola

Genes

2021 Volume 12, Issue 6

Abstract: Sjögren's Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic ... ...

Abstract	Sjögren's Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic regulations represent a link between genetic predisposition and environmental factors. Recent studies suggested a regulatory role for non-coding RNAs in critical biological and disease processes. Among non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a critical role in the post-transcriptional mRNA expression, forming a complex network of gene expression regulation. This review aims to give an overview of the latest studies that have investigated the role of miRNAs and lncRNAs in the SS. We included papers that investigated the expression of non-coding RNAs on different tissues, in particular on peripheral blood mononuclear cells and salivary glands. However, regarding the involvement of non-coding RNAs genetic variability in SS susceptibility very few data are available. Further research could help to elucidate underlying pathogenic processes of SS and provide new opportunities for the development of targeted therapies.
Language	English
Publishing date	2021-06-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes12060903
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Article ; Online: Large-scale DNA sequencing identifies rare variants associated with Systemic Lupus Erythematosus susceptibility in known risk genes.

Latini, Andrea / Borgiani, Paola / De Benedittis, Giada / Ciccacci, Cinzia / Novelli, Lucia / Pepe, Gerardo / Helmer-Citterich, Manuela / Baldini, Isabella / Perricone, Carlo / Ceccarelli, Fulvia / Conti, Fabrizio / Ianniciello, Generoso / Caceres, Juan / Ottalevi, Riccardo / Capulli, Mattia / Novelli, Giuseppe

Gene

2024 Volume 907, Page(s) 148279

Abstract: The identification of rare genetic variants associated to Systemic Lupus Erythematosus (SLE) could also help to understand the pathogenic mechanisms at the basis of the disease. In this study we have analyzed a cohort of 200 Italian SLE patients in order ...

Abstract	The identification of rare genetic variants associated to Systemic Lupus Erythematosus (SLE) could also help to understand the pathogenic mechanisms at the basis of the disease. In this study we have analyzed a cohort of 200 Italian SLE patients in order to explore the rare protein-coding variants in five genes (TNFAIP3, STAT4, IL10, TRAF3IP2, and HCP5) already investigated for commons variants found associated in our previous studies. Genomic DNA of 200 SLE patients was sequenced by whole exome sequencing. The identified variants were filtered by frequency and evaluated by in silico predictions. Allelic association analysis was performed with standard Fisher's exact test. Introducing a cutoff at MAF < 0.01, a total of 19 rare variants were identified. Seven of these variants were ultra-rare (MAF < 0.001) and six were absent in the GnomAD database. For TNFAIP3 gene, the variant c.A1939C was observed in 4 SLE patients and it is located in a region enriched in phosphorylation sites and affects the predict affinity of specific kinases. In TRAF3IP2 gene, we observed 5 different rare variants, including the novel variant c.G410A, located in the region that mediates interaction with TRAF6, and therefore a possible risk factor for SLE development. In STAT4 gene, we identified 6 different rare variants. Among these, three missense variants decrease the stability of this protein. Moreover, 3 novel rare variants were detected in 3 SLE patients. In particular, c.A767T variant was predicted as damaging by six prediction tools. Concluding, we have observed that even in genes whose common variability is associated with SLE susceptibility, it is possible to identify rare variants that could have a strong effect in the disease development and could therefore allow a better understanding of the functional domain involved.
MeSH term(s)	Humans ; Genetic Predisposition to Disease ; Lupus Erythematosus, Systemic/genetics ; Alleles ; DNA ; Sequence Analysis, DNA ; Polymorphism, Single Nucleotide
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2024-02-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2024.148279
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Article ; Online: KLRG1 is reduced on NK cells in SLE patients, inversely correlates with disease activity and is modulated by hydroxychloroquine

Novelli, Lucia / Barbati, Cristiana / Capuano, Cristina / Recalchi, Serena / Ceccarelli, Fulvia / Vomero, Marta / Alessandri, Cristiano / Morrone, Stefania / Conti, Fabrizio

Lupus

2023 Volume 32, Issue 4, Page(s) 549–559

Abstract: Objectives: Killer cell lectin-like receptor G 1 (KLRG1): Methods: Eighteen SLE patients and twelve healthy controls were enrolled. Peripheral blood mononuclear cells (PBMCs) from these patients were phenotypically characterized by immunofluorescence ...

Abstract	Objectives: Killer cell lectin-like receptor G 1 (KLRG1) Methods: Eighteen SLE patients and twelve healthy controls were enrolled. Peripheral blood mononuclear cells (PBMCs) from these patients were phenotypically characterized by immunofluorescence and flow cytometry. The effect of the hydroxychloroquine (HCQ) Results: KLRG1 expression was significantly reduced on the analyzed immune cell populations in SLE patients compared to HC, especially on total NK cells. Moreover, expression of KLRG1 on total NK cells inversely correlated with the SLEDAI-2K. A direct association between KLRG1 expression on NK cells and patients' treatment with HCQ was observed. Conclusion: With this study we revealed a reduced expression and an impaired function of KLRG1 on NK cells in SLE patients. These results suggest a possible role of KLRG1 in the pathogenesis of SLE and as a novel biomarker of this disease.
MeSH term(s)	Humans ; Hydroxychloroquine/pharmacology ; Hydroxychloroquine/therapeutic use ; Lupus Erythematosus, Systemic ; Leukocytes, Mononuclear/metabolism ; Killer Cells, Natural ; Flow Cytometry ; Receptors, Immunologic/metabolism ; Lectins, C-Type
Chemical Substances	Hydroxychloroquine (4QWG6N8QKH) ; KLRG1 protein, human ; Receptors, Immunologic ; Lectins, C-Type
Language	English
Publishing date	2023-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/09612033231160979
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Article ; Online: Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2.

Cantini, Fabrizio / Marchesoni, Antonio / Novelli, Lucia / Gualberti, Giuliana / Marando, Francesca / McDearmon Blondell, Erin / Gao, Tianming / McGonagle, Dennis / Salvarani, Carlo

Rheumatology (Oxford, England)

2024

Abstract: Objectives: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with psoriatic arthritis from the SELECT-PsA Phase 3 trials.: Methods: Patients with an inadequate response/intolerance to ≥ 1 non-biologic ... ...

Abstract	Objectives: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with psoriatic arthritis from the SELECT-PsA Phase 3 trials. Methods: Patients with an inadequate response/intolerance to ≥ 1 non-biologic DMARD (SELECT-PsA 1) or ≥ 1 biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution, and protection from enthesitis development through week 56. Results: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in > 80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. Conclusions: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. Clinicaltrials.gov identifiers: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae057
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Zs.MO 497: Show issues

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Article ; Online: PCSK3 Overexpression in Sjögren’s Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with IFN-γ Gene Expression

Latini, Andrea / De Benedittis, Giada / Colafrancesco, Serena / Perricone, Carlo / Novelli, Giuseppe / Novelli, Lucia / Priori, Roberta / Ciccacci, Cinzia / Borgiani, Paola

Genes (Basel). 2023 Apr. 26, v. 14, no. 5

2023

Abstract: Background: The PCSK3 gene encodes for the protease enzyme Furin, which promotes proteolytic maturation of important regulators of the immune response, and also enhances the secretion of interferon-γ (IFN). Several studies have suggested its possible ... ...

Abstract	Background: The PCSK3 gene encodes for the protease enzyme Furin, which promotes proteolytic maturation of important regulators of the immune response, and also enhances the secretion of interferon-γ (IFN). Several studies have suggested its possible involvement in the pathogenesis of chronic inflammatory diseases. Methods: We investigated the PCSK3 gene expression level in peripheral blood mononuclear cells isolated from Sjögren’s Syndrome (SS) patients and healthy controls and we evaluated a possible correlation with IFN-γ gene expression. Moreover, we also explored the variability of two PCSK3 genetic polymorphisms (rs4932178 and rs4702) to evaluate a possible association between these polymorphisms and the expression levels of this gene. Results: We observed, by RT-qPCR, that the PCSK3 expression level was significantly higher in SS patients compared to the controls (p = 0.028), and we confirmed a positive correlation between PCSK3 and IFN-γ expression levels (p < 0.001). Moreover, we reported that the variant homozygous genotype of rs4932178 SNP is associated with a higher expression of the PCSK3 gene (p = 0.038) and with the SS susceptibility (p = 0.016). Conclusions: Our data suggest that Furin could play a role in SS development, also promoting IFN-γ secretion.
Keywords	gene expression ; genes ; homozygosity ; immune response ; pathogenesis ; promoter regions ; proteinases ; proteolysis ; secretion
Language	English
Dates of publication	2023-0426
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14050981
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Co-Inheritance of Pathogenic Variants in PKD1 and PKD2 Genes Determined by Parental Segregation and De Novo Origin: A Case Report

Graziani, Ludovico / Zampatti, Stefania / Carriero, Miriam Lucia / Minotti, Chiara / Peconi, Cristina / Bengala, Mario / Giardina, Emiliano / Novelli, Giuseppe

Genes (Basel). 2023 Aug. 06, v. 14, no. 8

2023

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, and it is typically caused by PKD1 and PKD2 heterozygous variants. Nonetheless, the extensive phenotypic variability observed among affected individuals, ... ...

Abstract	Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, and it is typically caused by PKD1 and PKD2 heterozygous variants. Nonetheless, the extensive phenotypic variability observed among affected individuals, even within the same family, suggests a more complex pattern of inheritance. We describe an ADPKD family in which the proband presented with an earlier and more severe renal phenotype (clinical diagnosis at the age of 14 and end-stage renal disease aged 24), compared to the other affected family members. Next-generation sequencing (NGS)-based analysis of polycystic kidney disease (PKD)-associated genes in the proband revealed the presence of a pathogenic PKD2 variant and a likely pathogenic variant in PKD1, according to the American College of Medical Genetics and Genomics (ACMG) criteria. The PKD2 nonsense p.Arg872Ter variant was segregated from the proband’s father, with a mild phenotype. A similar mild disease presentation was found in the proband’s aunts and uncle (the father’s siblings). The frameshift p.Asp3832ProfsTer128 novel variant within PKD1 carried by the proband in addition to the pathogenic PKD2 variant was not found in either parent. This report highlights that the co-inheritance of two or more PKD genes or alleles may explain the extensive phenotypic variability among affected family members, thus emphasizing the importance of NGS-based techniques in the definition of the prognostic course.
Keywords	autosomal dominant polycystic kidney disease ; case studies ; genomics ; heterozygosity ; phenotype ; phenotypic variation
Language	English
Dates of publication	2023-0806
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14081589
Database	NAL-Catalogue (AGRICOLA)

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