Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Monogenic immune disorders provide unprecedented insights into the consequences of disrupting single genes in humans, thereby informing our understanding of fundamental immune function and disease. Genomics has accelerated monogenic disease discovery while also revealing the complexity of human disease, where several factors beyond the genome can govern pathogenesis. At this juncture, the optimal path forward will focus on maximizing basic and translational immunology insights from these disorders. This pursuit will be most direct and impactful if human disease gene discovery is paired with mechanistic studies employing integrative omics and mouse modeling to leverage their unique strengths.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915947 | PMC |
| http://dx.doi.org/10.1016/j.coi.2021.09.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form.
Methods: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan).
Severe Oral Lichen Planus Masking a Primary Immunodeficiency: X-Linked Lymphoproliferative Disease Type 1 (XLP-1).
Pediatr Dermatol
September 2025
Department of Dermatology, Hospital Sant Joan de Déu, Barcelona, Spain.
A 14-year-old boy was initially diagnosed with erosive oral lichen planus based on clinical and histopathological findings. However, the atypical clinical course and resistance to immunosuppressive therapy raised suspicion for an autoinflammatory disorder or inborn error of immunity. Genetic testing revealed a pathogenic SH2D1A mutation, confirming X-linked lymphoproliferative disease type 1 (XLP-1) in the absence of Epstein-Barr virus exposure.
View Article and Find Full Text PDFA Clinical Case Report of Deficiency of Adenosine Deaminase 2 Syndrome (DADA 2) Presenting as a Brachial Artery Aneurysm.
Mediterr J Rheumatol
March 2025
Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India.
Introduction: Deficiency of adenosine deaminase 2 (DADA 2) syndrome is a monogenic auto-inflammatory vasculitic syndrome caused by loss of function mutations in the ADA2 gene. Disease manifestations are divided into three major phenotypes: inflammatory/vascular, immune dysregulation, and haematologic, with majority having significant overlap between these phenotypes. The disease has undergone extensive phenotypic expansion since its first description in 2014.
View Article and Find Full Text PDFNovel COL4A3-COL4A5 variants and digenic inheritance in pediatric Alport syndrome from Southwestern China.
Sci Rep
August 2025
Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming Medical University, Kunming, Yunnan, 650228, China.
Alport syndrome is a hereditary glomerular disease driven by pathogenic variants in COL4A3-COL4A5 that compromise the α3-α4-α5 type IV collagen scaffold, manifesting as persistent hematuria, proteinuria, and ultimately end-stage renal disease. Its pronounced phenotypic variability, low sensitivity of renal biopsy, and limited response to ACE inhibitors complicate accurate diagnosis and therapy. In a cohort of 40 pedigrees from southwest China, we discovered 21 novel COL4A3-COL4A5 mutations.
View Article and Find Full Text PDFMaturity-onset diabetes of the young type 10 (MODY10) is a monogenic diabetes subtype caused by heterozygous mutations in the insulin gene (), leading to defective proinsulin processing, endoplasmic reticulum (ER) stress, and β-cell dysfunction. Current management relies on sulfonylureas or insulin therapy, but these fail to address the underlying genetic defect. Recent research has elucidated the molecular mechanisms of MODY10, including ER stress induced by proinsulin misfolding, activation of the unfolded protein response (UPR), and β-cell apoptosis.
View Article and Find Full Text PDF