Publications by authors named "S A Karabina"
A20 haploinsufficiency (HA20) is an autoinflammatory disease caused by heterozygous loss-of-function variations in , the gene encoding the A20 protein. Diagnosis of HA20 is challenging due to its heterogeneous clinical presentation and the lack of pathognomonic symptoms. While the pathogenic effect of truncating variations is clearly established, that of missense variations is difficult to determine.
View Article and Find Full Text PDFObjective: To identify the molecular basis of a severe systemic autoinflammatory disorder (SAID) and define its main phenotypic features, and to functionally assess the sequence variations identified in LYN, a gene encoding a nonreceptor tyrosine kinase.
Methods: We used targeted next-generation sequencing and in vitro functional studies of Lyn phosphorylation state and Lyn-dependent NF-κB activity after expression of recombinant Lyn isoforms carrying different sequence variations.
Results: We identified a de novo LYN variation (p.
Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome.
View Article and Find Full Text PDFArticle Synopsis
- A study was conducted on a family with a rare form of chronic urticarial lesions that are inherited dominantly and linked to elevated cytokine levels.
- Researchers used genetic analysis, whole-exome sequencing, and proteomic methods to identify the underlying causes and associated proteins related to the condition.
- The findings revealed a loss-of-function mutation in the RNF213 gene, affecting a protein called mysterin, which plays a significant role in regulating inflammation and understanding immune responses.
Objective: To identify the molecular basis of a systemic autoinflammatory disorder (SAID) evocative of TNF receptor-associated periodic syndrome (TRAPS).
Methods: (i) Deep next generation sequencing (NGS) through a SAID gene panel; (ii) variant allele distribution in peripheral blood subpopulations; (iii) in silico analyses of mosaic variants using TNF receptor superfamily 1A (TNFRSF1A) crystal structure; (iv) review of the very rare TNFRSF1A mosaic variants reported previously.
Results: In a 36-year-old man suffering from recurrent fever for 12 years, high-depth NGS revealed a TNFRSF1A mosaic variant, c.