Presentation: Patient of Cypriot descent with reduced renal function and microscopic haematuria

A 32-year-old male of Cypriot descent was referred to the local nephrology team with evidence of proteinuria and microscopic haematuria. The patient’s father and paternal aunt were investigated for declining renal function and both progressed to end-stage kidney disease requiring transplantation.

You should always consider genomics testing in cases where a patient has Cypriot ancestry and C3 glomerulopathy, unexplained haematuria or renal failure.

• Consult the National Genomic Test Directory. Here you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
• For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our Knowledge Hub resource ‘Genomic testing in the devolved nations’.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed-Off Panels Resource.
• Decide which of the tests best suits the needs of your patient/family:
  • R196 CFHR5 Nephropathy: This indication is for a single gene test and should be used for patients of Cypriot descent presenting with C3 glomerulopathy or unexplained haematuria or renal failure. It is undertaken via multiplex ligation-dependent probe amplification (MLPA) (or equivalent), that looks for variants in the CFHR5 gene that are associated with this phenotype.
  • R197 Membranoproliferative glomerulonephritis including C3 glomerulopathy: Use this indication for patients with idiopathic membranoproliferative glomerulonephritis (MPGN) or C3 glomerulopathy and a family history of MPGN or unexplained end-stage renal disease, or if renal transplant or complement inhibition is being considered, if R196 criteria is not met. This test includes MLPA and a small panel of genes known to cause MPGN.
  • R240 Diagnostic testing for known mutation(s): This indication can be used if a patient is clinically affected with CFHR5 nephropathy and also has a family member with a known pathogenic or likely pathogenic variant. In this situation, the laboratory will only test for the known familial variant.
  • R242 Predictive testing for known familial mutation(s): This indication is for a predictive (also known as presymptomatic) test and can be used for unaffected individuals who have a family member with a known pathogenic or likely pathogenic variant. It must be requested by clinical genetics.
• The tests listed above do not include whole genome sequencing (WGS). For these tests, use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
  • Parental samples may be needed for interpretation of the proband’s result, for example to determine whether a variant is de novo or inherited. These samples may be requested by the testing laboratory or you may wish to contact clinical genetics.
• Note that different forms are required for any test involving WGS.
• These tests are DNA-based, so an EDTA sample (purple-topped tube) is required.

For clinicians

• GeneReviews: C3 Glomerulopathy
• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• KDIGO: Clinical Practice Guideline for the Management of Glomerular Diseases
• NHS England: National Genomic Test Directory
• UK Kidney Association: MPGN, DDD & C3 Glomerulopathy

For patients

• UK Kidney Association: MPGN, DDD & C3 Glomerulopathy