Efficient Targeted Next Generation Sequencing-Based Workflow for Differential Diagnosis of Alport-Related Disorders

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...

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Bibliographic Details
Published in:PloS one 2016-03, Vol.11 (3), p.e0149241-e0149241
Main Authors: Kovács, Gábor, Kalmár, Tibor, Endreffy, Emőke, Ondrik, Zoltán, Iványi, Béla, Rikker, Csaba, Haszon, Ibolya, Túri, Sándor, Sinkó, Mária, Bereczki, Csaba, Maróti, Zoltán
Format: Article
Language:English
Subjects:
Adult
Alport syndrome
Autoantigens - genetics
Biology and Life Sciences
Biopsy
Child, Preschool
Children
Collagen
Collagen (type IV)
Collagen Type IV - genetics
Diagnosis
Diagnosis, Differential
Diagnostic systems
Differential diagnosis
Disease
DNA sequencing
End-stage renal disease
Female
Gene sequencing
Genes
Genetic analysis
Genetic aspects
Hematuria
Hereditary nephritis
High-Throughput Nucleotide Sequencing
Humans
Internal medicine
Kidney diseases
Life expectancy
Life span
Male
Medical diagnosis
Medicine
Medicine and Health Sciences
Methods
Middle Aged
Mutation
Nephritis, Hereditary - diagnosis
Nephritis, Hereditary - genetics
Pediatrics
Pedigree
Proteinuria
Renal failure
Research and Analysis Methods
Workflow
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Summary: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 We successfully identified mutations in all investigated cases, including 14 unpublished mutations in our Hungarian cohort.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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0149241