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Clinical Research

Genetic causes of FH

The All Wales FH Cascade Testing Service has been a major step forward for patients with inherited high cholesterol.  Genetic testing for alterations in FH genes (spelling mistakes in the genetic code) is an effective way of finding family members who also have FH.  To date, we have diagnosed FH using DNA testing in about 25% of the patients that we have tested.  This means that for 75% of people tested we are not able to provide a definite genetic diagnosis.  This may be because there are other changes in the DNA that we don’t yet know about or don’t yet test for.  The FH Research Team (Cardiff University) are working with the FH Clinical Team (doctors and nurses) to remedy this.  Two new studies are underway which aim to improve things.

Variants of Uncertain Significance Study (VUS Study)

MagGlassHelix Sometimes we identify a variant (spelling mistake) in one of the three main FH genes but cannot be sure if this is actually causing FH or not. These are called variants of uncertain significance (VUS).  A VUS is found in around 8% of index patients.  An index patient is the first person in a family who is diagnosed with FH. Currently, family DNA testing for VUS is not routinely offered because we don’t know if they are having an effect on cholesterol levels or not.
Kate Haralambos is coordinating a project for the families of index patients with a VUS to try and find out if a specific VUS causes high cholesterol.  This project is lead overall by Dr Ian McDowell with the support of all Lipid consultants and FH nurses in Wales.

Who can take part in the VUS study?

Kate will be working with the Clinical Care Team to contact patients with a VUS to offer genetic testing to their families and to assess whether the VUS tracks with cholesterol levels in the family.  This will help to determine whether the VUS is causing FH and improve the genetic diagnosis and treatment for that patient and their family.

To read more about this study you can download the participant information sheets:

Participant Information Sheet for FH Index Patients

Participant Information Sheet for Relatives of FH Index Patients

Cholesteryl Ester Storage Disorder (CESD) Study

Do other genetic alterations cause high cholesterol?
MagGlassHelix About two thirds of the index patients that we test for FH do not have any alteration detectable in the three main FH genes.  This does not mean that they don’t have a genetic cause of high cholesterol.  It just means that the genetic cause or causes of their raised cholesterol levels has not yet been found.  DNA samples from all patients that participate in the FH testing service are stored so that they can be re-tested if new genetic tests become available.
Recently, a condition called Cholesteryl Ester Storage Disorder (CESD), which also results from a genetic alteration, has been shown to resemble FH.   CESD increases the risk of early onset heart disease, but treatments are available to reduce this risk.  We are about to start a project that will use stored samples from FH index patients with ‘negative genetic results’ to find out how common the CESD alteration is in patients with inherited high cholesterol, but who do not have one of the common FH genes.


Who can take part in the CESD Study?

If you were the first person in your family to have an FH genetic test (index patient) and you had a ‘negative’ result then you can be tested for the CESD gene alteration.

The research team will need your consent to test your stored DNA sample.  You won’t need to come to clinic for this – it can be done by post.


Eligible patients will receive a study pack through the post from the clinical team.

You don't have to wait for this ....



If you want your sample to be included in the study you can download the CESD Study information sheet and study consent form, then complete and post the consent form to the research office:

FH Research, Room 102
Wales Heart Research Institute
Cardiff University
CF14 4XN


To speak to someone about either of these studies please contact:

Kate or Pauline on 02920 743864 or email:

Kate (VUS Study)

Pauline (CESD Study)


How can i get involved with FH Research in the future?



Only certain people will be eligible for the projects above, but from time to time we need help with other research.

Being involved with research doesn’t always mean taking part in the project.  We also value patient input when planning research and in developing research materials e.g. designing and writing the documentation that tells patients about the research we’re planning, in words and ways that are meaningful to them.


If you are interested in being involved in our future research please contact us:

FH Research, Room 102
Wales Heart Research Institute
Cardiff University
CF14 4XN

Phone: 02920 743864

Email: or

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