Improving genetic diagnosis in severe congenital neutropenia

Summary

Severe congenital neutropenia (SCN) is a blood disorder which causes deficiency of bacteria-fighting cells, leading to repeated life-threatening infections. Although SCN is an inherited condition caused by faulty genes, the exact genetic change cannot be confirmed in 75% of patients, including a family with 6 affected members cared for by UHBW. This means that these patients cannot be given accurate advice about how their disease is likely to progress, the risk of SCN occurring in their children and whether specific treatments are available.

New genetic testing technologies in the NHS now enable genetic faults to be detected rapidly and reliably. However, a major barrier to genetic diagnosis in SCN patients remains confirmation of whether individual genetic changes are the cause of SCN, or just innocent bystander changes. Scientists in Bristol and elsewhere have developed an efficient laboratory method for testing whether genetic changes in neutrophil genes are harmful by genetically altering stem cells from blood donations and then transforming these cells into neutrophils in the laboratory so that the effects of the genetic changes can be observed.

This research aims to refine this experimental system to make it suitable for use as a bespoke clinical diagnostic tool for SCN patients in which genetic testing has not given a diagnosis. We will provide proof-of-principle of the usefulness of this refined method by evaluating a change in a new gene identified in the large SCN family at UHBW through the NHS 100,000 Genomes Project. We hope that this research will enable genetic diagnosis and potential treatment options for the first time in this local family, but also provide essential pilot data to support future research aimed at testing the usefulness of this approach in larger groups of NHS patients.