Development of a new blood test for diagnosing the start of puberty
Research type
Research Study
Full title
Investigation of the utility of transcriptomic and epigenetic data for diagnosing the onset of puberty
IRAS ID
310719
Contact name
Beverly Hird
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Duration of Study in the UK
2 years, 8 months, 28 days
Research summary
Summary of Research
Children with early or late development of signs of puberty are referred to Paediatric Endocrinology at the Royal Manchester Children’s Hospital (RMCH) for investigations to distinguish relatively benign variants of development from disorders requiring treatment. These tests involve the child having a drip inserted into a vein, a medication is given via the drip and multiple blood samples are taken during the next hour. The medication given as part of the test can have side effects such as nausea, headache and abdominal pain. For children who have had many medical procedures in the past, siting the drip and getting the multiple blood tests can be difficult.
Our previous work has identified that we can use a single blood sample to measure gene expression levels (the activity of the genes) in the blood as an alternative way of diagnosing growth hormone deficiency. In this study we plan to investigate if the same approach can be used to diagnose disorders of puberty. A test based on a single blood sample without the need to administer medication via a drip would be much better for patients. In medical practice, the test would be useful if it could demonstrate if true puberty had started and was likely to progress.
This study will recruit children with early or late signs of puberty who are attending RMCH for a Gonadotrophin-releasing hormone (GnRH) test. As part of their routine clinical care a drip (intravenous cannula) will be inserted, and blood samples will be taken from this drip. For study participants an additional 5 mL of blood will be taken at the same time as the routine clinical bloods are collected. This extra blood sample will be used to analyse the gene expression and DNA methylation patterns. Data will be collected from the participants' medical records.Summary of Results
Some children are suspected of having early or delayed puberty and need a test to find out if puberty has started, to help doctors make recommendations about treatment. The test currently used involves having a medicine injected and 3 blood samples collected over an hour. Previously, researchers have measured the activity of genes in the blood (only one sample needed per patient) to diagnose children unable to make enough growth hormone in their bodies. The current study aimed to design a blood test for puberty, using patterns of gene activity or chemical tags on DNA called methylation.
Information on gene activity, DNA methylation and stage of puberty available in a large group of normal children (ALSPAC study) was used to look for patterns in the data using computer programmes. Factors found to be good at correctly predicting puberty stage were used to predict puberty in patients at Royal Manchester Children’s Hospital suspected of having early or delayed puberty. Patients were put into the pre-pubertal or pubertal group, based on the results of routine tests. The patterns of gene activity and DNA methylation were then used to see how well the computer could identify the correct group for each patient. Although the RMCH groups were small, the results are promising (all 32 children put in the correct group using gene activity and 41 out of 46 children put in the correct group using DNA methylation).REC name
North West - Preston Research Ethics Committee
REC reference
23/NW/0074
Date of REC Opinion
15 Mar 2023
REC opinion
Further Information Favourable Opinion