Routine genetic testing we offer

 

Rapid Sanger Sequencing

Sanger sequencing of the ABCC8 and KCNJ11 genes with a result issued within 1-2 weeks for newly diagnosed individuals and those who do not respond well to medical therapy.

 

Bespoke Whole Exome Sequencing

Whole exome sequencing is recommended for children who are showing a good response to medical therapy or for those where Sanger sequencing of ABCC8 and KCNJ11 does not identify a pathogenic variant. The panel includes all 21 genes currently listed as green on Genomics England PanelApp, R144 panel for Congenital Hyperinsulinism. This assay can also detect copy number variants.  A full list of the genes and non-coding regions captured on the Exeter Congenital Hyperinsulinism panel can be found here.

Methylation studies for Beckwith-Wiedemann Syndrome

We offer testing for Beckwith-Wiedemann syndrome using a methylation-specific MLPA assay that detects disturbances in methylation at the chromosome 11p15.5 region.

 

Prenatal testing including Non-Invasive Prenatal Testing (NIPT)

Prenatal testing through the Exeter Genomics Laboratory may be possible for families with congenital hyperinsulinism where knowledge of the fetal genotype impacts pregnancy management, delivery and immediate postnatal care.

The laboratory are also currently offering NIPT for some pregnant women where either they or the baby’s father has a confirmed diagnosis of HNF4A MODY.

Individual cases should be discussed with Dr Jayne Houghton (jaynehoughton@nhs.net) with further information regarding this service found here.

Who can we test?

Our laboratory is a global referral centre for Congenital Hyperinsulinism genetic testing.

England, Wales and Northern Ireland

For individuals living with Congenital Hyperinsulinism in England, Wales, and Northern Ireland genetic testing is offered through the R144 NHS service.

International Referrals

We welcome global referrals for genetic testing. Please contact the laboratory to discuss all referrals, prior to sending samples.

For families who are unable to access testing, either through their own healthcare provider or by personal means, it is possible to apply for funding to cover the associated costs through the Open Hyperinsulinism Genes project. This initiative is funded by Congenital Hyperinsulinism International. Please contact Prof Sarah Flanagan at S.Flanagan@exeter.ac.uk to discuss the eligibility of individuals cases.

What referral documentation should you send with the samples?

Prior to sending samples to our laboratory a completed clinical request form should be returned via email.  A copy of this form should also be included with the samples from the patient and both parents.

What Samples are required?

Please send samples from the patient and both parents if possible. We accept fresh blood samples, extracted DNA or pancreatic tissue samples.

Blood: Please send at least two 4ml EDTA blood samples (1ml minimum for neonates, 5-10ml for children and 10-20ml for adults). Samples should be transported at ambient (room) temperature. Blood samples in glass bottles are not accepted by the laboratory. Blood samples should be received by our laboratory within 5 days of venesection. Do not freeze blood samples – if storage is required prior to dispatch, blood samples can be stored at 4ºC (39.2ºF).

Extracted DNA: Please send a minimum of 5μg of DNA. DNA samples can be sent at room temperature.

Formalin-Fixed, Paraffin-Embedded (FFPE) Tissue: To test for loss of maternal heterozygosity of chromosome 11p15.5-11p15.1 in focal hyperinsulinism please send a minimum of 10 x 10μm of FFPE tissue from the pancreatic lesion. This should be sent at room temperature and with prior arrangement with the laboratory.

Other: In special circumstances, a saliva sample is acceptable. Please contact the laboratory if you require sample collection kits (GeneFix). Please contact the laboratory prior to sending any other samples.

How do I send samples?

Samples should be sent via first-class post or courier at ambient (room) temperature. All packaging must comply with UN3373 regulations governing the packaging and transport of biological samples. Full details can be found here.

1. The sample should be wrapped in enough tissue to absorb the entire contents of the tube in the event of a breakage.

2. Seal the tissue with tape and place it into a specimen bag and seal.

3. Samples should then be placed in a sample box or padded envelope along with a copy of the referral information and the package marked ‘Pathological Specimen – Fragile With Care’.

Please send samples to:

The Exeter Genomics Laboratory,

RILD Building Level 3,

Royal Devon University Hospital,

Barrack Road,

Exeter, EX2 5DW, UK

How will I know when the samples have arrived?

The referring clinician or laboratory will receive an automated email from the laboratory as soon as the samples are booked onto our LIMS system. This is usually within 48 hours of the samples arriving in Exeter.

When will genetic reports be issued?

This depends on the testing being performed. Reports detailing the results of rapid analysis of the KATP channel genes are usually issued within 5-10 working days of the sample arriving in our laboratory. Results of other tests such as targeted exome sequence will take longer to become available (e.g. up to 8 weeks).

Reports will be issued to the referring healthcare professional, as per the Association of Clinical Genomic Science (ACGS) guidelines. We can not send genetic reports directly to patients or their families.

Research Studies

 

We are recruiting individuals for gene discovery studies. Using Wellcome Trust funds, we will perform whole genome sequencing to search for new genetics causes of this condition. Individuals with a clinical diagnosis of congenital hyperinsulinism that has persisted for more than 6 months are eligible to enrol in this study when genetic testing of the known congenital hyperinsulinism genes has not identified a disease-causing variant. A detailed clinical history is required along with samples from the affected individual, parents and affected/unaffected siblings. This should be sent from the individual’s doctor. Further information regarding this project can be obtained by emailing Prof Sarah Flanagan (s.flanagan@exeter.ac.uk).

Incidental findings

Whilst the strategies that we employ result in a low prior probability of identifying variants that predispose to other rare diseases it is possible that these variants will be found. Our policy on incidental findings is to report only results pertaining to the congenital hyperinsulinism in the patient.

Consent for Research

Individuals who consent to research will be recruited to the Genetic Beta Cell Research Bank. The Genetic Beta Cell Research Bank is a tissue bank with over-arching ethics to carry out research into the mechanisms and genetic causes of diabetes and other beta cell disorders.

Consent should be obtained at the time of sample collection and should comply with your own institution’s policies. Our consent form can be used for this purpose if required. The completed form can be stored locally or sent with the samples for storage in the Exeter laboratory.