Autoinflammatory Diseases: Germline vs. Somatic Mosaic Variations - Maladies génétiques d'expression pédiatrique
Poster De Conférence Année : 2024

Autoinflammatory Diseases: Germline vs. Somatic Mosaic Variations

William Piterboth
Florence Dastot Le Moal
Farah Diab
Rahma Mani
Romain Levergeois

Résumé

Background/Objectives: The study primarily investigates somatic mosaic variations within systemic autoinflammatory diseases (SAID) genes and their correlation with disease phenotypes, specifically focusing on variations in NLRP3 and TNFRSF1A leading to NLRP3-AIDs and TRAPS (Tumor necrosis factor-Receptor-Associated Periodic Syndrome) respectively. Methods: From 2018 to 2023, deep-targeted NGS was used to analyze the leukocyte DNAs of 800 patients using a SAID gene panel. All mosaic variations in SAID genes from PubMed and Infevers databases were reviewed. Results: In NLRP3, 9 mosaic variations were identified in 12 independent patients, along with 10 germline variations in 10 patients. The literature reports 34 mosaic and 88 germline NLRP3 variations. Phenotype: genotype correlations suggest that NLRP3 variations found only somatically may be incompatible with life if present germinally, while variations found only in germinal state could be asymptomatic in mosaic state. In TNFRSF1A, two mosaic variations were found in three patients. The literature reports only three other mosaic variations. No obvious difference in disease severity between germline and mosaic variations has been observed. Very few mosaic variations have been reported in the literature in other SAID genes: NLRC4 (n=4), STING1 (n=2), NOD2 (n=2), and JAK1 (n=1), precluding any genotype: phenotype correlation studies. Most of mosaic variations identified in SAID genes were found to be widely distributed across different tissues. Conclusion: The study underscores the high frequency of mosaic variations in NLRP3-AIDs and emphasizes the symptomatic nature of mosaic variations, even at very low allele frequencies (below 5%), potentially leading to false-negative diagnostic tests without deep sequencing
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Dates et versions

inserm-04674708 , version 1 (21-08-2024)

Identifiants

  • HAL Id : inserm-04674708 , version 1

Citer

Eman Assrawi, Elma El Khouri, Camille Louvrier, William Piterboth, Florence Dastot Le Moal, et al.. Autoinflammatory Diseases: Germline vs. Somatic Mosaic Variations. European Society of Human Genetics, Jun 2024, Berlin (Germany), Germany. ⟨inserm-04674708⟩
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