Following the recent development of genetic testing for SRNS causative gene mutations using Next Generation Sequencing (McCarthy, et al 2013), clinical genetic testing is now offered via the Bristol Clinical Genetics Laboratory.
Who should be tested?
All patients with SRNS with any of the following:
- Primary steroid resistance (i.e. no or incomplete response to steroids after 4 weeks of high dose steroids)
- Extra-renal manifestations
- A positive family history
- Presentation in the 1st three months of life
- And no evidence of a secondary cause (e.g. obesity, hypertension, HIV)
Services offered by Bristol Genetics Laboratories
- 37 genes are targeted using a custom designed HaloPlex Target Enrichment System kit and sequenced using a MiSeq (Illumina) analyser.
- Familial tests are available for known mutations using Sanger sequencing.
The Service has UKGTN approval, and there is (currently capped) funding via central commissioning to pay for this test in the NHS.
Sending blood to Bristol Genetics Laboratories
All genetic testing requires consent. It is the responsibility of the referring clinician to ensure that appropriate consent has been obtained.
DNA is stored from all patients unless consent for this is specifically denied. These samples are used for quality assurance purposes and may be used anonymously for development of new tests for the relevant disorder.
Adults: 5mls blood in EDTA tube
Paediatric: minimum of 1ml but preferably >2mls in EDTA tube
Include details of test, family history, address, postcode, NHS number, referring clinician and unit/hospital
What if a pathogenic mutation is found?
If a pathogenic genetic mutation is found then consider rapid withdrawal of immunosuppression (Büscher et al, 2010). There are occasional case reports of patients with WT1 mutations responding to ciclosporin (Gellermann et al 2010; Wasilewska, Kuroczycka-Saniutycz & Zoch-Zwierz, 2011) and if the patient has a COQ10 pathway mutation, then COQ10 supplements should be initiated (Heeringa, 2011; Montini, Malaventura & Salviati, 2008).