Spliceosomal Disorders

  • Research type

    Research Study

  • Full title

    Understanding the role of U5 snRNP gene mutation in pre-messenger RNA splicing and craniofacial development



  • Contact name

    William Newman

  • Contact email


  • Sponsor organisation

    Central Manchester University Hospitals NHS Foundation Trust (CMFT)

  • Duration of Study in the UK

    2 years, 2 months, 31 days

  • Research summary

    Summary of Research

    This study is part of the Musketeers memorandum - a national agreement relating to rare disease projects, which prevents a full review of protocol and the need for individual negotiations by each NHS trust taking part in the said study. This means we will easily be able to roll the study out across other UK sites as a multi-centre study.

    Gene splicing is a method by which our DNA is chopped up by proteins to remove introns and leave behind the coding DNA which provides the template for important proteins to be made.
    Mis-regulation of splicing can be an important feature of many human diseases.
    These disorders can be caused by changes in genes that interfere with splicing or by splicing not taking place in the first place.

    Given that these disorders are very rare, many behaviours and features of people affected by these conditions have not been identified and explained yet. We believe that this may have a big effect in managing the care of patients with such conditions.

    As part of this study, we wish to:

    - Describe the characteristics of groups of patients with isolated or syndromic ENT (Ear/ Nose/ Throat) anomalies
    - Find out how common these changes are in people with isolated or syndromic ENT anomalies
    - Identify new genes responsible for spliceosomal disorders and isolated ear/nose/throat anomalies
    - Explain the scientific role of the proteins programmed by spliceosomal genes

    To achieve these aims we will:

    - Look for shared gene changes in consanguineous families
    - Use various DNA sequencing techniques including - Sanger, targeted, whole exome or whole Genome sequencing

    Summary of Results

    The study was undertaken to find the cause of a very rare form of health problem apparent at birth or in early childhood resulting in hearing loss, blockage of the back of the nose (choanal atresia) and changes in facial appearance. We identified a number of individuals with these health problems and undertook genetic testing. In two study participants we identified the specific changes in the gene that was responsible for their health problems. For these individuals the results provided a definite explanation for their health problems and information for other family members.
    We did not find the genetic cause for the other individuals in the study suggesting that their health problems may have a more complicated genetic explanation.

  • REC name

    North West - Greater Manchester East Research Ethics Committee

  • REC reference


  • Date of REC Opinion

    3 Mar 2017

  • REC opinion

    Further Information Favourable Opinion