Genetic Testing for IEIs in the United Kingdom
Genetic testing for inborn errors of immunity (IEI) in England is provided by the NHS England Genomics with analysis undertaken by genetics laboratories in London (Great Ormond Street Hospital) and Manchester (Manchester University Hospital). This testing aims to diagnose and manage immune deficiency and dysregulation disorders, which can significantly improve the life expectancy and health-related quality of life for affected individuals1.
Currently the main options are whole genome sequencing as a trio with analysis of a virtual gene panel (R15). Detailed, updated information about the NHS Genomics R15 panel for primary immunodeficiency or monogenic inflammatory bowel disease can be found on the Genomics England website.
For urgent cases an agnostic R14 whole genome trio can be undertaken (14 days TAT) or a WES for the R15 genes (14-21 day TAT). In addition, targeted genetics testing is available for a number of IEIs (see NHS England » National genomic test directory for current list). The above are all fully funded under NHS England for NHS England eligible patients. The WES R15 and targeted testing can be offered on a paid basis for those not eligible under the NHS.
The genetics labs work closely with the immunology labs to enable protein expression and functional testing to direct genetic analysis or help clarify variants of unknown significance. Regional and national multi-disciplinary team meetings are held to discuss unusual findings.
New born screening for SCID (Trecs) is being piloted in 6 English NBS labs with a decision about national rollout due end of 2025. There is a study (Generation Study – Generation Study) of the utility of WGS on 100,000 newborns reporting mutations in 200+ diseases.
As health is a devolved matter, options in Northern Ireland, Wales and Scotland differ slightly. All Wales Medical genomics services runs a R15 following NHS England guidelines (Microsoft Word – PD-GEN-R15_WES). NHS Grampian offer combined primary immunodeficiency and rheumatology testing (gen-form-215-primary-immunodeficiency-request-form-for-genetic-testing.pdf).Patients in Northern Ireland may be eligible for genome and exome sequencing though a clinical genetics referral (GENI: Genome and Exome sequencing Northern Ireland | Belfast Health & Social Care Trust website).
For more detailed information, you can visit the https://www.england.nhs.uk/genomics/
Report prepared by: Kimberley Gilmour (Department of Immunology, Great Ormond Street Hospital (GOSH), London, UK) and Sophie Hambleton (Newcastle’s Great North Children’s Hospital)
