PT  - JOURNAL ARTICLE
AU  - Ilenia Simeoni
AU  - Olga Shamardina
AU  - Sri VV Deevi
AU  - Moira Thomas
AU  - Karyn Megy
AU  - Emily Staples
AU  - Deborah Whitehorn
AU  - Daniel Duarte
AU  - Rutendo Mapeta
AU  - Willem H Ouwehand
AU  - Christopher J Penkett
AU  - Paula Rayner-Matthews
AU  - Hannah Stark
AU  - Jonathan C Stephens
AU  - Kathleen E Stirrups
AU  - Ernest Turro
AU  - NIHR BioResource
AU  - Adrian Thrasher
AU  - Taco W Kuijpers
AU  - Kenneth GC Smith
AU  - Sinisa Savic
AU  - Siobhan O Burns
AU  - James E Thaventhiran
AU  - Hana Lango Allen
TI  - GRID – Genomics of Rare Immune Disorders: a highly sensitive and specific diagnostic gene panel for patients with primary immunodeficiencies
AID  - 10.1101/431544
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 431544
4099  - http://biorxiv.org/content/early/2019/01/15/431544.short
4100  - http://biorxiv.org/content/early/2019/01/15/431544.full
AB  - Primary Immune disorders affect 15,000 new patients every year in Europe. Genetic tests are usually performed on a single or very limited number of genes leaving the majority of patients without a genetic diagnosis. We designed, optimised and validated a new clinical diagnostic platform called GRID, Genomics of Rare Immune Disorders, to screen in parallel 279 genes, including 2015 IUIS genes, known to be causative of Primary Immune disorders (PID). Validation to clinical standard using more than 58,000 variants in 176 PID patients shows an excellent sensitivity, specificity. The customised and automated bioinformatics pipeline prioritises and reports pertinent Single Nucleotide Variants (SNVs), INsertions and DELetions (INDELs) as well as Copy Number Variants (CNVs). An example of the clinical utility of the GRID panel, is represented by a patient initially diagnosed with X-linked agammaglobulinemia due to a missense variant in the BTK gene with severe inflammatory bowel disease. GRID results identified two additional compound heterozygous variants in IL17RC, potentially driving the altered phenotype.