Novel nonsense mutation in COL4A4 associated with Alport syndrome

Abstract

Mutations are the major cause of genetic disorders. Development of next generation sequencing techniques have played a vital role in the identification of mutations in the patients which help us to relate specific mutations to various disorders. In an effort to identify and correlate mutations to Alport syndrome, whole exome sequencing and Sanger sequencing were carried out in a family having significant family history of Alport syndrome on maternal side. Since mutations in collagen encoding genes, especially COL4A3, COL4A4 and COL4A5 are known to cause Alport syndrome, various in-silico tools were used to screen for deleterious mutations in these genes. Here we report a novel mutation in COL4A4, Lys1688 to stop gain mutation in the patient. Analysis of the mutation using various databases revealed that this mutation occurs in a highly conserved region of COL4A4 protein and also it is predicted to be deleterious. Structural analysis and comparison of the mutant protein with wild type protein using in-silico tools also predict that the mutant protein has loss of function and could lead to the pathophysiology of the Alport syndrome.