Change in delivery of Neurology Rare Disease Clinical Indications
Dear Colleagues
I would like to inform you of a change in service delivery for some Neurology rare disease genomic tests in the East GLH region as part of the Genomic Medicine Service. The associated Rare Disease Test Directory Clinical Indications are listed in Table 1 below.
Whole Genome Sequencing (WGS) is now the preferred strategy for delivering diagnostic testing for these Neurology Clinical Indications. Improvements to the WGS analysis workflow mean that analysis of short tandem repeat (STR) disorders can now also be performed alongside small variant and copy number variant analysis. This improved workflow will provide a standalone WGS test for patients, supporting streamlined testing in the East GLH and will provide the opportunity for patients to participate in the National Genomic Research Library.
This change in delivery strategy means that NGS gene panel testing will no longer be available for these Neurology Clinical Indications and that STR testing using targeted PCR will only be available for certain disorders.
Diagnostic Testing
From the 23rd January 2023, WGS will be used for diagnostic testing of patients referred for the Neurology Clinical Indications listed in Table 1. STR expansions that are identified near to or above the normal size threshold will be confirmed using PCR testing prior to reporting. Analysis and reporting of WGS will be performed by both the Cambridge and Nottingham Clinical Scientist Teams using standardised processes and reporting templates.
After the 23rd January 2023, samples received for gene panel testing without a WGS specific test order will be extracted, stored and no testing will be performed. A report will be issued requesting the WGS test order process is completed (see below).
To support this transition, testing patients using targeted PCR will remain available for the common STRs until April 1st 2023 (Table 1, column 4). We recommend that this testing pathway is only used for patients with a high likelihood of a specific STR disorder.
Some Neurology Clinical Indications in the Test Directory list STR as the only associated test and therefore these will remain available to order as standalone PCR tests (Table 2). Furthermore, where there is strong clinical suspicion of Friedreich ataxia or X-Linked Spinal and Bulbar Muscular Atrophy type 1 (Kennedy’s disease), in addition to a family history consistent with the mode of inheritance of the disorder, then PCR testing will remain available for these patients (Table 2).
A list of all disorders associated with STR expansions are listed in Table 3.
Familial Testing for STR disorders
Testing for known familial STR disorders will be delivered using targeted PCR tests at the East Genomics Laboratory Hub or a partner Genomic Laboratory Hub.
WGS ordering requirements
Clinical Indications delivered by WGS must be ordered using a WGS test order form or using the WGS specific CUH EPIC process. A WGS Patient Choice Record of Discussion Form (consent form) must be completed and sent to the laboratory for each individual tested.
We recognise that the ordering process for WGS is a notable change to current practise. We have collated details of the Clinical Indications and instructions for referral, including flow charts, test order forms and remote consenting guidance, on the East GLH website: https://www.eastgenomics.nhs.uk/for-healthcare-professionals/genomic-tests/rare-andinherited-diseases/genome-sequencing/
Training for the Patient Choice Consent Framework is available online and should be completed prior to ordering WGS: https://elearning.cam-pgmc.ac.uk/course/index.php?categoryid=13 (opens in a new tab)
Please contact the Cambridge Genomics Laboratory with any queries, feedback or to request additional training for ordering WGS using the email address emee.glh@nhs.net (please include ‘Rare Disease WGS’ in the subject heading).