Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine

Abstract

Background: Alport syndrome is a primary basement membrane disorder arising from mutations in genes encoding the type IV collagen protein family. It is a genetically heterogeneous disease with different mutations and forms of inheritance that presents with renal affection, hearing loss and eye defects. Several new mutations related to X-linked forms have been previously determined. Methods: We report the case of a 12 years old male and his family diagnosed with Alport syndrome after genetic analysis was performed. Result: A new mutation determining a nucleotide change c.3614G . T (p.Gly1205Val) in hemizygosis in the COL4A5 gene was found. This molecular defect has not been previously described. Conclusion: Molecular biology has helped us to comprehend the mechanisms of pathophysiology in Alport syndrome. Genetic analysis provides the only conclusive diagnosis of the disorder at the moment. Our contribution with a new mutation further supports the need of more sophisticated molecular methods to increase the mutation detection rates with lower costs and less time.

Ocular Manifestations and Potential Treatments of Alport Syndrome: A Systematic Review

“…AS is inherited and mainly induced by a mutation within one of the collagen genes; COL4A3 and COL4A4 are located on chromosome 2 while COL4A5 is located on the X -chromosome [ 2 ]. The X -linked form of the disease is the most common, representing nearly 80% of all AS cases, while the autosomal forms of the disease, which can be dominant or recessive depending on the gene variant, account for the remaining 20% [ 2 , 3 ]. Moreover, while males are typically more severely affected, females who are heterozygous for COL4A5 variants will still present symptoms that are typically milder and show a slower progression compared to males [ 2 , 3 ].…”

“…The X -linked form of the disease is the most common, representing nearly 80% of all AS cases, while the autosomal forms of the disease, which can be dominant or recessive depending on the gene variant, account for the remaining 20% [ 2 , 3 ]. Moreover, while males are typically more severely affected, females who are heterozygous for COL4A5 variants will still present symptoms that are typically milder and show a slower progression compared to males [ 2 , 3 ]. The COL4A3 , COL4A4 , and COL4A5 genes encode collagen IV α 3, α 4, and α 5 chains, respectively [ 2 ].…”