Novel COL4A5 mutation in preimplantation genetic diagnosis of a patient with Alport syndrom

Abstract Purpose We report a novel gene mutation in a female patient with Alport syndrome who was planning to undergo assisted reproduction to achieve pregnancy. We performed pathogenicity analysis on the mutation and selected a suitable assisted reproductive technology solution for the patient.Methods A retrospective analysis of clinical and genetic data of a patient with Alport syndrome was performed. Whole-exome data of the COL4A5 gene of the patient’s family were analyzed using Sanger sequencing and online software was used to predict the conservation and pathogenicity of mutant amino acids within species evolution.Results The patient planned assisted reproductive technology due to secondary infertility and unexplained hematuria. Urine test results revealed 60% severely deformed red blood cells, indicating persistent glomerular hematuria. Renal biopsy revealed that the basement membrane was of varying thickness, with a thickened dense layer, some of which was tear-like and arachnoid. Foot processes showed segmented fusion and the basement membrane was torn under electron microscopy. Genetic analysis revealed an unnamed mutation in the COL4A5 gene, c.3188G>A, which resulted in amino acid changes (p.Gly1063Asp). This was verified as a new mutation not present in the parents, whereas the daughter had a heterozygous mutation. Biological information analysis revealed the mutation was pathogenic and preimplantation genetic diagnosis was adopted. Eventually the patient gave birth to a full-term daughter without the gene mutationConclusion Genetic testing prior to pregnancy is recommended in Alport syndrome patients or family members prior to pregnancy to determine the specific location of the gene mutation. Patients should receive genetic counseling, fertility guidance, and assisted reproduction advice from experts in heredity.