Alport autossômica: um estudo de duas famílias norte-rio-grandenses

Abstract

Alport syndrome (AS) is a genetically rare, heterogeneous and hereditary pathology associated with germline mutations in collagen type IV genes (COL4A3, COL4A4 and COL4A5). Characterized by progressive loss of renal function, hearing and eye damage during early childhood, the progression of the disease progresses to a terminal renal disease often associated with renal failure. Studies aimed at early diagnosing individuals with this nephropathy may lead to appropriate treatment and thus improve life expectancy. Efforts are currently underway, focused on the genome of patients, to create diagnostic tests for rare diseases/syndromes. From this perspective, mutations, genes and metabolic pathways involved with the pathology is crucial to understanding the complexity of these diseases. Thinking about corroborating the findings and studies about AS, the exome sequencing of two families from Rio Grande do Norte (RN), both composed of four individuals, was performed. Through the GATK and VARSCAN2 software, variants were called followed by a screening of deleterious variants identified by an in house script. The results pointed to two novels deleterious variants in the genes that form the type IV collagen α3 and α4 chains (a stop codon in COL4A3 and frameshift in COL4A4) leading to premature protein truncation. Both variants were detected in homozygous state in the probands and heterozygous in the other family members. Additionally, a broad region of Runs of Homozigosity (ROH) involving the COL4A3 and COL4A4 genes was detected in both probands of both families. According to the findings of deleterious variants in the COL4A3 and COL4A4 genes in ROH regions, these variants are now related to SA so that similar observations can serve as support for possible targets in the creation of new diagnostic tests and for the service of Genetic Counseling.