Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era DOI Open Access
Conor J. O’Donovan, Lay Teng Tan,

Mohd Azri Zainal Abidin

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(15), P. 4435 - 4435

Published: July 29, 2024

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors immunity characterised by defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective inflammatory complications. Despite recent advances our understanding genetic molecular pathophysiology X-linked autosomal recessive CGD, growth availability functional testing, there remain significant barriers early accurate diagnosis. In current review, we provide an up-to-date summary CGD pathophysiology, underpinning methods diagnostic testing for closely related disorders. We present overview benefits diagnosis when suspect test CGD. discuss historical NADPH oxidase activity, as well assays measuring protein expression subunits. Lastly, focus on genomic employed diagnose including gene-targeted panels, comprehensive ancillary methods. Throughout, highlight general limitations caveats specific interpretation results context disorders, outlook newborn screening future.

Language: Английский

Gene therapy for inborn errors of immunity: current clinical progress DOI
Sathi Wijeyesinghe, Javier Chinen

Annals of Allergy Asthma & Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review DOI Creative Commons
Mohammad Salehi, Zeinab Neshati, Hamid Ahanchian

et al.

Health Science Reports, Journal Year: 2025, Volume and Issue: 8(3)

Published: March 1, 2025

ABSTRACT Background and Aim Hyper IgE syndromes (HIES) are rare primary immunodeficiency characterized by susceptibility to specific infections, eczema, elevated levels. Pathogenic mutations in STAT3 , IL6R IL6ST ERBB2IP PGM3 ZNF431, SPINK5, TGFBR1/2 CARD11 have been identified as genetic factors contributing phenotypes of HIES lead hindered differentiation activity, aberrant signaling cascades disrupting immune regulation. present a diverse clinical symptoms, challenging diagnosis management; understanding its pathophysiology, genetics, immunological abnormalities offer hope for improved outcomes. In this review we aim provide comprehensive the condition also discuss latest updates on pathological features, spectrum variability, abnormalities, inheritance patterns, new candidate genes, challenges, management strategies, epidemiology future directions HIES. Methods This conducted an extensive search information from multiple databases, including PubMed, Scopus, WHO, ClinVar ensure coverage. Preference was given articles published recently capture research developments. Endnote employed reference manager. The relevant literature meticulously reviewed address objectives study. Results Missense, nonsense, frameshift variants commonly observed Understanding these is key diagnosing managing conditions such Hyper‐IgE recurrent infection (linked IL6R, STAT3, ZNF341 mutations), Atopy associated with ERBIN which links TGF‐β pathway, Immunodeficiency 23 (caused Netherton syndrome (resulting SPINK5 Loeys‐Dietz (related TGFBR mutations). Each year, genes responsible type deficiency added list. Conclusion Although rare, significantly impacts patients due complex medical manifestations need lifelong management. Identifying casual essential effective conditions.

Language: Английский

Citations

0
Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation DOI Creative Commons
Iris Ramos-Hernández, Carla Fuster‐García, Araceli Aguilar-González

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(8)

Published: April 22, 2025

Abstract To improve ex vivo gene therapy strategies involving hematopoietic stem and progenitor cells (HSPCs), we propose a novel knock-in strategy (named KI-Ep) aiming to achieve transgene regulation of the inserted cassette through acquisition naturally occurring epigenetic marks. Based on this hypothesis, selected CX3CR1 (a myeloid-specific presenting poised histone signature primitive HSPCs) as safe harbor generate KI-Ep HSPCs. We demonstrated that, unlike expression pattern achieved with lentiviral vectors (LVs), insertion constitutive into intron 1 locus (CX3CR1-I) in HSPCs resulted very low levels more but, crucially, strong HSPC-differentiated populations (especially myeloid cells), both vitro vivo. Furthermore, showed that promoter CX3CR1-I acquired marks associated genes during HSPC stage. These transitioned activated states upon differentiation. In summary, here, introduce concept which enables modulation cell stages its subsequent activation

Language: Английский

Citations

0
Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era DOI Open Access
Conor J. O’Donovan, Lay Teng Tan,

Mohd Azri Zainal Abidin

et al.

Published: July 18, 2024

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors immunity characterised by defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective inflammatory complications. Despite recent advances our understanding genetic molecular pathophysiology X-linked autosomal recessive CGD, growth availability functional testing, there remain significant barriers early accurate diagnosis. In current review, we provide an up-to-date summary CGD pathophysiology, underpins methods diagnostic testing for closely related disorders. We present overview benefits diagnosis when suspect test CGD. discuss historical NADPH oxidase activity, as well assays measuring protein expression subunits. Lastly, focus on genomic employed diagnose including gene-targeted panels, comprehensive ancillary methods. Throughout, highlight general limitations caveats specific interpretation results context disorders, outlook newborn screening future.

Language: Английский

Citations

1
[Advances in gene therapy for inborn errors of immunity]. DOI
Ting Li, Hongmei Song

PubMed, Journal Year: 2024, Volume and Issue: 26(8), P. 865 - 870

Published: Aug. 15, 2024

Inborn errors of immunity (IEI) are a diverse group disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With rapid development molecular biology, specific pathogenesis many has been revealed, making gene therapy possible preclinical clinical research this type disease. This article reviews advancements for IEI, aiming to increase awareness understanding these disorders.

Language: Английский

Citations

1
Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era DOI Open Access
Conor J. O’Donovan, Lay Teng Tan,

Mohd Azri Zainal Abidin

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(15), P. 4435 - 4435

Published: July 29, 2024

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors immunity characterised by defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective inflammatory complications. Despite recent advances our understanding genetic molecular pathophysiology X-linked autosomal recessive CGD, growth availability functional testing, there remain significant barriers early accurate diagnosis. In current review, we provide an up-to-date summary CGD pathophysiology, underpinning methods diagnostic testing for closely related disorders. We present overview benefits diagnosis when suspect test CGD. discuss historical NADPH oxidase activity, as well assays measuring protein expression subunits. Lastly, focus on genomic employed diagnose including gene-targeted panels, comprehensive ancillary methods. Throughout, highlight general limitations caveats specific interpretation results context disorders, outlook newborn screening future.

Language: Английский

Citations

0