Research Highlights




New genetic test leads to faster, more accurate diagnosis of childhood eye disorders


A new test to help diagnose and predict a range of serious childhood eye conditions has been developed by researchers at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health (ICH). 


The gene panel test, known as Oculome, screens for mutations in more than 400 genes that are known to lead to eye disease, including those that can cause malformations of the eyeball and those linked to inherited retinal degeneration and cataracts. It was developed by Professor Jane Sowden's research group at ICH and the GOSH Genetics Laboratory led by Dr Lucy Jenkins. Read more...




FH-CPSS project results are published


N Engl J Med 2016;375:1628-37.




FH-CPSS project passes the 10,000 samples mark


The Child-Parent Screening Study is being run by Professor David Wald at The Wolfson Institute of Preventive Medicine.  It is a new approach to screen for Familial Hypercholesterolaemia (FH) that is based on measuring cholesterol in children aged 1-2 years when they attend for routine childhood immunisation.


Cholesterol levels and genetic tests are being carried out in 10,000 children, with the genetic analysis being carried out in the regional genetics lab at GOSH.  Over 10,000 samples have now been tested.

This research study will determine the accuracy of screening by this method and the feasibility of a national screening programme.





100,000 Genomes Project - Genomics England (GEL)


Overall objective:


11 centres across England have been designated as Genomics Medicine Centres (GMC) and will work closely with Genomics England (GEL) and NHS England (NHSE) to deliver the required 100,000 samples for whole genome sequencing.


 The samples will be categorised as:


1) Rare Disease: Patients and their parents are required for Trio analysis


2) Cancer: For each patient, tumour and blood samples are required for the project


The Role of GOSH:


GOSH is the lead centre for the North Thames Genomics Medicine Centre (NTGMC) that includes the following centres:


  • Great Ormond Street (NTGMC Lead) - Rare disease only
  • North West London Hospitals (KGC) - Rare disease & Cancer
  • Neurogenetics Laboratory (ION) - Rare disease only
  • Moorfields Eye Hospital (MEH) - Rare disease only
  • The Royal Free Hospital (RFH) - Rare disease only
  • UCL Advanced Diagnostics (UCL-AD) - Cancer only
  • Barts and the London (Barts) - Rare disease & Cancer


The NTGMC has been contracted to provide 14,808 DNA samples for whole genome sequencing over the three year project.


As the designated lead, all samples from across North Thames will be sent to GEL via our lab in Barclay house.  The regional genetics lab will receive samples from our local delivery partners.




Prenatal Assessment of Genomes & Exomes - PAGE Study


We are participating in the PAGE study which aims to improve the prenatal diagnosis of fetal structural abnormalities by evaluating the role of exome and genome sequencing and developing cost-effective assays using these new technologies.


Women undergoing invasive diagnostic testing in participating units will be asked for informed consent for any excess chorionic villi or amniocytes to be used for the PAGE study.


In addition both parents will be asked to donate a blood sample as we will be sequencing trios.


The aim is to recruit 1000 trios (mother, father and fetus) for exome sequencing, around 40 of which will be selected for whole genome sequencing as well. Any woman undergoing invasive diagnostic testing with an NT>4mm or one or more sonographic abnormality is eligible for recruitment.


Exome sequencing will be done at the Sanger Institute. Any pathogenic results will be validated in the two coordinating regional centres. Results will be reviewed by a review panel including representative from clinical, molecular and cytogenetics from participating laboratories. Pathogenic results with implications for families will be fed back to families through their local regional genetics services. Results will not be available in the course of the research, but any that have clinical relevance to future pregnancies will be reported after the pregnancy is completed.


MARCH 2014


Experts back prenatal Down's syndrome blood test


Leading scientists have given their backing to introducing a 99% accurate blood test to detect Down's syndrome in unborn babies on the NHS. In a new development, a scientific impact paper published by the Royal College of Obstetricians and Gynaecologists (RCOG) supports giving the test to all women who want it in early pregnancy.


Non-invasive prenatal testing (NIPT) can predict whether a baby has Down's and also screens for the rare genetic conditions Edward's syndrome and Patau syndrome. NIPT is currently only available in private hospitals but is being considered for use on the NHS by the UK National Screening Committee, which will make a formal recommendation once the results of a trial at Great Ormond Street Hospital for Children in London become known. The trial is being undertaken as part of the RAPID (Reliable Accurate Prenatal Non-Invasive Diagnosis) research programme led by Professor Lyn Chitty.




Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study


Research published in The Lancet provides new evidence that a substantial proportion of individuals with a clinical diagnosis of Familial Hypercholesterolaemia (FH) inherit a combination of small-effect changes in several genes (polygenic) rather than a large-effect mutation in a single gene (monogenic). These findings have implications for the majority of national guidelines on family screening for FH that advocate testing relatives of all individuals with a clinical diagnosis of FH, including those of the UK National Institute for Health and Care Excellence (NICE).


"Cascade [family] testing of the roughly 40% of patients with a clinical diagnosis of FH and an identifiable causative mutation would eliminate staff and screening costs associated with screening relatives of the remaining 60% of patients without an identifiable mutation. This is very likely to be more cost-effective, but proving this will require a more detailed analysis", says British Heart Foundation Professor Steve Humphries from University College London, who led the research.


FH is one of the most common inherited disorders affecting over 12 million people worldwide (1 in 500 of the general population). It causes very high levels of low-density lipoprotein cholesterol (LDL-C) or "bad cholesterol" in the blood, and if untreated, results in a five to eight times greater risk of early coronary heart disease (CHD). Identification of patients with FH needs to be improved because at least 75% of cases remain undetected, untreated, or improperly treated, despite good evidence that early detection and treatment with statins can significantly improve life expectancy. 


DNA-based cascade screening to identify other family members with FH, who would  benefit from treatment, has been recommended by NICE on the presumption of a monogenic inheritance of the disorder, where first-degree relatives would have a 50:50 chance of having the condition. However, 60% of people with clinically suspected FH have no identifiable mutation in any of the three genes (LDLR,APOB, orPCSK9) known to cause FH.


"The current study was designed to investigate whether individuals who inherit many, small-effect, LDL-C raising sequence differences in a wide range of genes might have received a clinical diagnosis of FH, which would influence the efficacy of any cascade screening programme since the odds of finding relatives with grossly elevated LDL-C in such cases would be less than the expected 50%", explains Humphries.


Recent genetic studies have identified many common genetic variants associated with a small increment in LDL-C levels. Genotyping for 12 of these single nucleotide polymorphisms (SNPs) was done on blood samples from 321 mutation-negative UK patients with FH, as well as 319 UK patients with FH with a known mutation, and 3020 healthy individuals (controls) from the UK Whitehall II study.


Each participant was assigned a weighted LDL-C-raising gene score based on the number of risk-associated gene copies inherited. The results were validated by repeating the analysis in a sample of over 700 patients with FH from Belgium.


The findings showed that clinically suspected, but mutation negative FH, was associated with inheritance of a greater than average number of small-effect LDL-C-raising sequence differences.


According to Humphries, "We propose that the clinical diagnosis of FH should be restricted to those in whom a mutation can be identified, whereas those with no detected mutation should be given the clinical diagnosis of polygenic hypercholesterolaemia. Both groups of patients will need statin therapy, but the cost effectiveness of FH cascade testing will differ depending on whether or not there is a polygenic or a single mutation cause."




© 2011 Great Ormond Street Hospital for Children NHS Trust