Characteristics of the test: (includes 26 genes)

General characteristics of the clinical phenotype

The nephrotic syndromes are characterised with massive proteinuria, hypoalbuminuria and oedema. This is a heterogeneous group of disorders resulting from impaired function of the podocytes in the glomeruli and increased penetrance of the renal filter. In children, several histological sub-types of the disease can be distinguished such as minimal-change nephropathy, focal segmental glomerulosclerosis and diffuse mesangial proliferative glomerulonephritis. It has been found that the response to corticoid treatment rather than the histological characteristics of each patient have better prognostic value for the disease progression. Thus, nephrotic syndromes are often classified as steroid-sensitive (SSNS, quick resolution of the proteinuria following initiation of therapy) and steroid-resistant (SRNS, treatment is not associated with remission). In rare cases SRNS is associated with anomalies of the development of the genitourinary tract and/or Wilms’ tumours (Denys-Drash OMIM #194080 and Fraser OMIM # 136680 syndromes; neprhoblastoma or Wilms’ tumour OMIM # 194070).

The steroid-resistant form of the disease is diagnosed in app. 10% of the nephrotic syndrome patients and is associated with increased risk of complications. Most of the cases are due to genetic mutations and the extended panel of 24 genes allows the identification of pathogenic variants in the majority of the patients. 

Reasons for referring:

All patients with steroid-resistant nephrotic syndrome.

Interpretation of results:

• Identification of point mutations and small deletions/insertions in the genes included in the panel will lead to genetic diagnosis and will help the clinical team to choose the best suited treatment for you or your child; 

• The screening method employed does not allow reliable identification of large deletions and insertions. For this kind of analysis we recommend that this test is combined with suitable CNV detection test (MLPA, aCGH);

• Our genetic counsellor will interpret the result for you and will answer any questions you may have.

Method: Next generation sequencing (MiSeq, Illumina).

The method involves bidirectional DNA sequencing of all coding exons and intron-exon boundaries of the target genes. The laboratory offers single exon sequencing for establishing the carrier status of close relatives of patients with known mutations (Test № 128, 129).

Sensitivity of the method: depends on the GC/AT content of the respective sequences, as well as the presence of duplicated segments. 

What does the test involve?

• DNA isolation and sample storage.

• Parallel sequencing of the target genes.

• Bioinformatic analysis of the sequencing data. Only the target genes of interest for the patient will be analysed. 

• Preparation of written result from the genetic test.

• Diagnostic interpretation of the results and genetic counselling.

Biological material: Venous blood of DNA

For more information, please read "Biological Sample Requirements and Transport Information" carefully.