Renal Disease

Genomics and Pathology Services (GPS) offers germline variant detection by next-generation sequencing in key genes implicated in a variety of renal diseases.

Results can provide physicians with useful information to make more definitive diagnoses in order to better manage their patients. They also enable tailored genetic counseling in both the patient and at-risk family members.

REQUISITIONINFO SHEETGENES


Indications for Testing

Indications for testing include symptoms of:

  • aHUS/TMA/C3 Glomerulopathy
  • Alport Syndrome
  • Cystic disease and Nephronophthisis
  • Nephrotic Syndrome and Focal Segmental Glomerulosclerosis

Available Tests and Gene Lists

aHUS/TMA/C3 Glomerulopathy Gene Set

13 genes sequenced include ADAMTS13, C3, CD46, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, DGKE and THBD; CFHR3-CFHR1 deletion by MLPA.

Alport Syndrome Gene Set

3 genes sequenced include COL4A3, COL4A4 and COL4A5.

Cystic disease and Nephronophthisis Gene Set

23 genes sequenced include AHI1, CEP290, GLIS2, INVS, IQCB1, NEK8, NPHP1, NPHP3, NPHP4, RPGRIP1L, TMEM67, TTC21B, XPNPEP3, BICC1, CRB2, EYA1, HNF1B,
PAX2, PKD1, PKD2, PKHD1, SIX5
and UMOD.

Nephrotic Syndrome and Focal Segmental Glomerulosclerosis Gene Set

34 genes sequenced include ACTN4, ADCK4 (COQ8B), ANLN, APOL1, ARHGAP24, ARHGDIA, CD2AP, COL4A3, COL4A4, COL4A5, COQ2, COQ6, CRB2, CUBN, EMP2, INF2, ITGA3, ITGB4, LAMB2, LMX1B, MEFV, MYH9, MYO1E, NEIL1, NPHS1, NPHS2, PDSS2, PLCE1, PTPRO, SCARB2, SMARCAL1, TRPC6, TTC21B and WT1.


Testing Methodology

Tests are performed using targeted hybridization capture coupled with next-generation sequencing (NGS) in our CAP/CLIA labs for comprehensive coverage of all coding exons of ordered genes.

Types of variation detected include single nucleotide variants (SNVs) and small insertions and deletions (indels).


Results and Interpretation

DNA sequence data are analyzed by GPS’ clinically validated bioinformatics pipeline to identify and annotate genetic variants associated with the phenotype(s).

Variants are interpreted by a board-certified clinical genomicist in the context of the patient’s disease. Those that are most likely to account for the observed clinical phenotype based on evidence from the medical literature are highlighted.

Results are returned to the ordering physician in a concise report.

The turnaround time for testing and interpretation is four to six weeks from the time a specimen arrives.


Specimen Requirements

Specimen types accepted include 2-5 mL peripheral blood in a lavender-top EDTA tube. Specimen collection kits are available upon request.

Request specimen kit »


Clinical Utility

Many times, a renal biopsy is simply not enough to make a definitive diagnosis – even when combined with the powerful ancillary techniques of immunofluorescence and electron microscopy.

 

This is particularly true in pediatric patients who present with steroid resistant nephrotic syndrome, and in patients with suspected complement system abnormalities such as atypical hemolytic uremic syndrome (aHUS).

Next-generation sequencing can provide clinicians with a powerful tool to manage patients with these diagnostically challenging renal diseases.