NCM 2022: Confirming a large complex structural variant using long read sequencing: a case study
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Here we present a case study of a 13-month-old boy referred for further investigations after presenting with bacterial meningitis (H Influenzae), despite having full immunisations. Subsequent immunological investigations identified a low to absent response to protein and conjugate polysaccharide vaccines, their identical twin brother similarly showed a comparable lack of antibody response. Extended Functional immune investigations have since taken place over the last 16 years along with genomic investigations, including exome and whole genome sequencing via the 100,000 genomes project. With little success, the patients have yet to obtain a formal diagnosis of their condition but hold a working molecular diagnosis of common immune pathway defect. A recent GECIP review of the 100,000 genomes project whole genome sequencing data identified a novel large complex structural variant (SV); an inverted duplication triplication event on chromosome 6, thought to impact the TNFAIP3 gene and predicted to cause defective production of NFKB1-dependent cytokines. Due to the size and complexity we are unable to characterise the SV using the short read sequencing data.