Molecular genetics and clinical analysis of X-linked dominant Alport syndrome caused by a new mutation of COL4A5 gene c.4518_c.4519 insC

ObjectiveTo analyze the collagen type Ⅳ α 5 chain(COL4A5) gene, provide the basis for molecular diagnosis and genetic counseling of a family with X-linked hereditary Alport syndrome, and investigate the COL4A5 gene shift mutation spectrum and clinical phenotype of Alport syndrome.

MethodsThe whole exome sequencing was used for gene detection, and Sanger sequencing was used to validate candidate pathogenic variants.

ResultsThe renal damage of patient progressed gradually, the gross hematuria and nephrotic syndrome appeared.The proteinuria and gross hematuria could be relieved after anti-infection treatment.The pathological biopsy of the kidney of the proband showed that the thickness of the basement membrane varied, the thickness of the dense layer increased, and parts were torn or cobweb.The results of high-throughput sequencing and first-generation sequencing indicated the exon 49 of COL4A5 gene, c.4518_c.4519 heterozygous variants of insC(p.gln1507profs *14) in patient was found, and neither parent carried the mutation.

ConclusionsIt is the first report that the new variation of COL4A5 gene at this locus is the pathogenesis of patient, which enrichs the spectrum of COL4A5 gene variation, and provides the basis for the molecular diagnosis and prenatal diagnosis of this family of X-linked hereditary nephritis.It is of great significance to guide the reproduction of mother and daughter in the family, and prevent the disease through prenatal genetic diagnosis or preimplantation genetic diagnosis.