Mammalian type IV collagen is a family of 6 chains that form three kinds of heterotrimeric molecules, which assemble into networks in basement membranes. Mutations in the COL4A3, COL4A4, or COL4A5 genes that prevent the normal assembly of a345(IV) collagen in the glomerular basement membrane (GBM) cause a spectrum of nephropathies with diverse clinical presentation. The most severe is Alport syndrome, a common hereditary nephropathy characterized by progressive kidney failure, hearing loss and ocular abnormalities. Heterozygous mutation in COL4 genes are variably implicated in autosomal dominant Alport syndrome, and thin membrane nephropathy. All forms of Alport syndrome are associated with focal and segmental glomerulosclerosis. Certain mutations in COL4A1 also cause nephropathy along with multi-organ involvement in HANAC syndrome.
Mutations in the COL4A3 - COL4A5 genes are the commonest cause of inherited kidney failure after polycystic kidney disease. No specific therapies for Alport syndrome exist yet. More specific therapies remain an unmet need. Progress in this area will require a better understanding of the pathogenic mechanisms though a combination of in vivo studies in animal models, in vitro studies, and in silico modeling. This Research topic provides a forum to present new data or new viewpoints, exchange ideas, and stimulate dialogue among investigators in this field.
This Research Topic welcomes the submission of Mini-Reviews, Reviews, Original Research, Brief Research Reports, or Perspectives articles including but not limited to the following topics:
• Advances in the diagnosis and prognosis on COL4 nephropathies
• Novel therapies for Alport syndrome
• Specific aspects of Alport syndrome in women
• COL4 mutations: Impact on collagen IV protein assembly, structure and function; and genotype-phenotype relationships
• Abnormal GBM composition, abnormal cell-matrix interactions, and podocyte stress in COL4 nephropathies
• Mechanistic insights from in vivo, in vitro, and in silico models
• Heterozygous COL4 mutations causing thin GBM disease, "autosomal dominant AS", and FSGS
• COL4A1/A2-related nephropathies (HANAC)
• COL4 variants as modifiers in other kidney diseases
• Variability and heterogeneity of COL4 nephropathies: Genetic and non-genetic modifiers
