13 genes sequenced include ADAMTS13, C3, CD46, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, DGKE and THBD; CFHR3-CFHR1 deletion by MLPA.
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.
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
Complement-mediated Renal Disease panel
Alport Syndrome panel
3 genes sequenced include COL4A3, COL4A4 and COL4A5.
Cystic disease and Nephronophthisis panel
33 genes sequenced include ACE, AGT, AGTR1, AHI1, BBS10, BICC1, CC2D2A, CEP290, CRB2, DNAJB11, EYA1, GANAB, GLIS2, HNF1B, INVS, IQCB1, MUC1, NEK8, NPHP1, NPHP3, NPHP4, PAX2, PKD1, PKD2, PKHD1, REN, RPGRIP1L, SIX5, TMEM67, TTC21B, UMOD, USH2A and XPNPEP3.
Nephrotic Syndrome and Focal Segmental Glomerulosclerosis panel
52 genes sequenced include ACE, ACTN4, ADCK4 (COQ8B), ANLN, APOL1, ARHGAP24, ARHGDIA, CD2AP, CLCN5, COL4A3, COL4A4, COL4A5, COQ2, COQ6, CRB2, CUBN, EMP2, FAT1, INF2, ITGA3, ITGB4, KANK1, KANK2, KANK4, LAGE3, LAMB2, LMX1B, MAGI2, MEFV, MYH9, MYO1E, NEIL1, NPHS1, NPHS2, NUP10, NUP205, NUP93, OCRL, OSGEP, PDSS2, PLCE1, PTPRO, REN, SCARB2, SMARCAL1, TP53RK, TPRKB, TRPC6, TTC21B, WDR73, WT1 and XPO5.
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).
For some cases with negative results or isolated heterozygous mutations in recessive genes, additional testing by alternate methodology will be performed to determine the presence of rare variant types not detected by this assay.
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 types accepted include 2-5 mL peripheral blood in a lavender-top EDTA tube or 2-4 buccal swabs (please contact laboratory prior to sending buccal swabs). Specimen collection kits are available upon request.
***Already extracted DNA can be accepted only with laboratory approval. The isolation of nucleic acids for clinical testing must have occurred in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or the CMS.
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.