Early Diagnosis of Inherited Immune Deficiency

  • Research type

    Research Study

  • Full title

    Bringing Next Generation Sequencing to the Next Generation: Early Diagnosis of Inherited Immune Deficiency

  • IRAS ID

    155667

  • Contact name

    Sophie Hambleton

  • Contact email

    sophie.hambleton@ncl.ac.uk

  • Sponsor organisation

    Newcastle upon Tyne Hospitals NHS Foundation Trust

  • Clinicaltrials.gov Identifier

    BH121334, Organisation's own funding reference

  • Duration of Study in the UK

    2 years, 8 months, 0 days

  • Research summary

    For children born with a faulty immune system, pinpointing the gene responsible can help predict problems and select the right treatment. Linking the faulty gene to the resulting pattern of disease can also teach us about what is important for human immunity. Yet the genetic diagnosis remains unknown in half of immunodeficient patients at our specialist centre. In this research study we propose to apply a new DNA sequencing method in 200 such children, WES or “Whole Exome Sequencing”, which screens for changes in all genes at once. We will develop and test ways of picking out the relevant genetic changes and compare the new method with current standard investigations in terms of speed and effectiveness.

    We expect Whole Exome Sequencing to show many patients to have mistakes in genes that are already linked to immunodeficiency. Potential advantages of the new technique will be its ability to detect types of genetic change that are invisible on standard testing and potentially also the speed with which relevant genes can be screened.

    Other patients will lack causative changes in known disease genes. We will study the results of their Whole Exome Sequencing further to discover new genetic causes of primary immunodeficiency. We will test how strongly the suspect genetic change links to disease within the family and the wider population. We will try to find out how it interferes with normal immune function by experiments in the test tube. In the current project we will set up a powerful new method to grow up white blood cells from patient skin samples. This will maximize what can be learnt about the faulty immune system, without subjecting patients to lots of blood tests. As soon as a linked genetic change is confirmed, this can be fed back to the clinical team and inform patient care.

  • REC name

    North East - Newcastle & North Tyneside 2 Research Ethics Committee

  • REC reference

    15/NE/0192

  • Date of REC Opinion

    30 Jun 2015

  • REC opinion

    Favourable Opinion