Fibronectin Glomerulopathy Without Typical Renal Biopsy Features in a 4-Year-Old Girl with Incidentally Discovered Proteinuria and a G417V FN1 Gene Mutation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 641 - 641

Опубликована: Янв. 14, 2025

Fibronectin glomerulopathy (FG) is caused by fibronectin 1 (FN1) gene mutations. A renal biopsy was performed on a 4-year-old girl with incidentally discovered proteinuria (150 mg/dL); her family history of disease negative. Markedly enlarged glomeruli (mean glomerular diameter: 196 μm; age-matched controls: 140 μm), α-SMA-positive and Ki-67-positive mesangial cell proliferation (glomerular index 1.76), the mild expansion areas, no immune or electron-dense deposits, normal basement membrane, diffusely effaced foot processes were observed. Genetic testing identified de novo heterozygous mutation (Gly417Val) in collagen-binding site FN II-2 domain, prompting immunostaining. Strong positivity noted, hence FG diagnosed. The follow-up period 29 months revealed nephrotic range proteinuria, intermittent microhematuria, hyperfiltration, preserved function. features early childhood-onset compared to case lobular pattern diagnosed 44-year-old patient undulating hypertension known for year, positive history. Early characterized enlargement, proliferation, changes that suggested deposition disease. In summary, novel aspects located at FN1 gene, not earlier, histologic spectrum expanded observed proliferative striking glomerulomegaly. Now, should also be considered among monogenic causes proteinuric kidney diseases pediatric nephrology practice.

Язык: Английский

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Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription

Acta Neuropathologica, Год журнала: 2025, Номер 149(1)

Опубликована: Янв. 16, 2025

Язык: Английский

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Hereditary non-spherocytic hemolytic anemia with GPI mutations successfully treated with allogeneic hematopoietic stem cell transplantation: a first report of two cases

Journal of Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Язык: Английский

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Deciphering the role of IL17RA in psoriasis and chronic mucocutaneous candidiasis: shared pathways and distinct manifestations

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Introduction Psoriasis and chronic mucocutaneous candidiasis (CMC), although distinct in their clinical manifestations, often coexist within specific patient cohorts. Despite this intriguing observation, genetic etiologies have been studied separately, neglecting the shared inflammatory mediator, interleukin 17A-F (IL17A-F). Consequently, immunogenetic foundations underlying these conditions remained enigmatic. Methods In study, we analyzed case of a 5-year-old female born to consanguineous parents who presented with concomitant psoriasis CMC phenotypes. Utilizing whole exome transcriptomic sequencing, meticulously investigated underpinnings molecular pathways complex pathologies. RNA sequencing was performed on skin biopsy confirm profiles associated conditions. Results We identified novel bi-allelic variant (NM_014339.6, c.1173C>G A) 17 receptor type A (IL17RA) gene, resulting premature stop codon (p. Tyr391Ter). truncation, our investigations revealed that produces fully functional IL17RA protein. This evident from presence patient’s peripheral blood mononuclear cells (PBMCs) ability mutant dimerize both wild-type protein its partners IL17RC IL17RD. Transcriptomic analysis showed psoriasis-associated signature intertwined pathways, including responses fungal infections. Discussion report unveils an unprecedented link serving as common denominator for CMC. The highlights pivotal role Our findings bridge critical knowledge gap provide insights into mechanisms connecting diseases. discovery not only advances understanding pathophysiology but also lays groundwork personalized therapeutic strategies, heralding new era precision medicine patients

Язык: Английский

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Di-Genic Inheritance in Genodermatoses: Insights from Two Consanguineous Cases in a Reference Lebanese Center within the Middle East and North Africa (MENA) Region

Dermatology Practical & Conceptual, Год журнала: 2025, Номер 15, С. 4935 - 4935

Опубликована: Янв. 21, 2025

Introduction: Genodermatoses refer to a group of heterogenous rare genetic diseases with cutaneous expression. Several genodermatoses present multisystem involvement that can range from mild life-threatening conditions leading increased morbidity and mortality. Objective: Given the paucity in literature field especially Middle East North Africa (MENA) region building up on first established database based Lebanon, this article aimed decipher basis 2 different types skin-inherited (androgenic alopecia vitiligo). Methods: Herein, we propose di-genic model inheritance which could be responsible for these diseases, using Whole Exome Sequencing (WES) GEO datasets. Results: We identified gene variants FOXC1(p.His484Tyr) SMARCD1 (p.Arg351Cys) androgenic HPS1(p.Ser566Ter) ITK (p.Pro521Leu) vitiligo. Further analysis datasets, confirmed connectivity between genes involved each disease. Conclusion: This study novel candidate disease explain underlying phenotypes open doors better-guided genomic approach personalized treatment early diagnosis.

Язык: Английский

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