title: Efficient Targeted Next Generation Sequencing-Based Workflow for Differential Diagnosis of Alport-Related Disorders.
abstract: Alport syndrome (AS) is an inherited type IV collagen nephropathies characterized by microscopic hematuria during early childhood, the development of proteinuria and progression to end-stage renal disease. Since choosing the right therapy, even before the onset of proteinuria, can delay the onset of end-stage renal failure and improve life expectancy, the earliest possible differential diagnosis is desired. Practically, this means the identification of mutation(s) in COL4A3-A4-A5 genes. We used an efficient, next generation sequencing based workflow for simultaneous analysis of all three COL4A genes in three individuals and fourteen families involved by AS or showing different level of Alport-related symptoms. We successfully identified mutations in all investigated cases, including 14 unpublished mutations in our Hungarian cohort. We present an easy to use unified clinical/diagnostic terminology and workflow not only for X-linked but for autosomal AS, but also for Alport-related diseases. In families where a diagnosis has been established by molecular genetic analysis, the renal biopsy may be rendered unnecessary.
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Kovács
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kalmár
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Emőke
authors.initials: E
authors.lastname: Endreffy
authors.affiliation: University of Szeged, Faculty of Medicine, First Department of Internal Medicine, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ondrik
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pathology, Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Iványi
authors.affiliation: Péterfy Sándor Hospital Department of Internal Medicine 1, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Rikker
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Haszon
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Túri
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Sinkó
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Bereczki
authors.affiliation: University of Szeged, Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Maróti
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000235:genetics*; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D057188:Workflow
chemical_list: D001324:Autoantigens; C466620:COL4A4 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain