Peripheral blood KIT Mutations in paediatric mastocytosis
Research type
Research Study
Full title
Identification and significance of peripheral blood KIT mutations in children with mastocytosis
IRAS ID
183807
Contact name
Clive Grattan
Contact email
Sponsor organisation
Guy's and St Thomas' NHS Foundation Trust
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Mastocytosis is a condition in which there is an accumulation of specialized cells containing histamine, called mast cells, in various tissues. It can be limited to the skin (cutaneous mastocytosis) or mast cells can accumulate throughout the body including the bone marrow (systemic mastocytosis). Adult-onset mastocytosis usually persists for the lifetime of the patient. By contrast, childhood mastocytosis is usually limited to the skin and improves substantially or resolves before puberty.
Most cases of adult mastocytosis are associated with somatic mutations in the KIT gene. The most common mutation is called D816V. This is located in KIT exon 17. Analysis of the KIT gene from the skin biopsies of 50 children found mutations in exon 17 in 42% of cases and mutations outside exon 17 in 44%.
Highly sensitive next generation sequencing has now been developed to detect the D816V mutation in the blood as well as from skin and bone marrow biopsies. A recent study looked at patients with suspected systemic mastocytosis who had tested negative for the D816V mutation in blood samples. Mutations were found in a different location (exon 8) in 18% of paediatric cases but in less than 1% of adult cases.
We would like to use these techniques to analyse blood samples from children with mastocytosis and determine the mutation levels over time in relation to any changes in clinical phenotype. The results will provide parents with more information on their child’s condition and will help to indicate whether more large scale genetic studies may be helpful in order to understand the role of mutations in paediatric mastocytosis.
REC name
London - Westminster Research Ethics Committee
REC reference
18/LO/0334
Date of REC Opinion
6 Apr 2018
REC opinion
Further Information Favourable Opinion