The Birman Heart FundLois Wilkie did a talk at the Birman Cat Club Show in 2015 and you can download the recording below Recording November 2017 - A message from our Researcher Update
from Lois Wilkie from the 2016 AGM
BIRMAN
CARDIOMYOPATHY RESEARCH UPDATE June 2018 update
We have been asked about our research progress and we thought to send
you a short update on what we have been working on and the plans for the
near future.
We have finally submitted 30 Birman samples for target gene sequence
to Edinburgh Genomics. It took us more time than initially expected
to submit all these samples, as we had to select the very best DNA
samples and this required several weeks of work in the lab. The
samples are now being sequenced and we should receive these results
in the next 3 months. We will then have to use high-power computing
to analyse the data, ie, we will be looking for mutations that may
have caused cardiomyopathy in the affected cats. This analysis is
complex and can take up to 6-9 months, but we are hoping this will
lead to a breakthrough with finding a mutation.
Regarding the 2nd stage of our study (Whole Genome SNP Array, very
generously funded) we still need to collect more samples. As
with the 1st stage of the project, we need high quality samples to
increase our chances of success (we need to have a larger number of
affected cats and normal, elderly cats). We have been contacted in
the last few months by several interested Birman breeders and
owners who would like their cats scanned. However, most people would
like us to scan off-site and this is always a bit challenging, as we
have a limited manpower for off-site scans and we can only scan
off-site if there are at least 3-4 cats per area. It is always much
easier for us and we have more flexibility in terms of days/times of
scanning if cats can come to our main hospital (QMHA).
Thanks so much for all your help and support for our projects –it is
greatly appreciated!
We will keep you posted on any new results.
Jose Novo Matos
Spring 2017 Over the past 18 months the study’s investigators
have screened 162 Birmans for heart disease. They found a high prevalence of
cardiomyopathy (heart muscle disease) in Birman cats (10%). Birman cats seem
to be affected by several different types of cardiomyopathy, such as
hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and
arrhythmogenic right ventricular cardiomyopathy (ARVC). However, HCM was the
most common type of cardiomyopathy in their population, affecting nearly 7%
of the Birman cats that they screened. This type of cardiomyopathy causes
thickening of the walls of the heart.
HCM was most commonly diagnosed in adult cats
(median age of 8.4 years), as previously described in other feline HCM
studies. This means that cats may develop HCM later in life and a normal
heart scan at a young age does not exclude the possibility of a cat
developing HCM at a later stage. Serial heart scans and exclusion of HCM
in previous generations is required to properly exclude this disease.
Heart murmurs appear to be more common in Birmans
with cardiomyopathy (heart muscle disease) than in healthy cats.
Although heart murmurs are not always a reliable indication of heart
disease in other breeds, the investigators findings suggest that any
Birman cat with a heart murmur should be investigated further for heart
disease with echocardiography. In cases of HCM, the septal wall of the
heart was most commonly thickened, which is typical of humans with
inherited HCM. Males were more frequently affected with HCM in their
study population (82% of the HCM cats were male), as repeatedly shown in
feline and human HCM studies. Eleven Birmans that died of heart disease
were submitted for pathological analysis, and similarly to the heart
scan results they found evidence of different forms of cardiomyopathy,
including HCM, RCM, ARVC and dilated cardiomyopathy (DCM). In humans,
these types of cardiomyopathy are usually associated with different
genetic mutations, but occasionally one genetic mutation can cause
multiple types of disease. They have identified families of Birmans that
include cats with HCM and RCM, and cats with HCM and ARVC. It is
possible that there is more than one mutation in these families, but it
is also possible that one mutation in a Birman family can result in
different types of cardiomyopathy.
The investigators have also investigated blood tests that can help identify cats with heart disease (cardiac ‘biomarkers’). Levels of these cardiac biomarkers are increased in the bloodstream when the heart chamber walls are under strain (shown by the biomarker ‘NT-proBNP’) or when heart muscle cells are damaged (shown by the biomarker ‘troponin-I’). These biomarkers do not appear to be helpful in all breeds when screening for cardiomyopathy, but they do appear to be helpful in Birmans. As there is an overlap in biomarker levels between healthy and affected cats, biomarkers will not be reliable enough to act as the sole test in screening breeding cats. Biomarkers may be useful however in determining which cats should be investigated further with echocardiography. Early diagnosis of more severely affected cats will allow cats to be started on treatment to reduce the risk of blood clots (‘aortic thromboembolism’), which is a devastating and often fatal complication of cardiomyopathy. They have built a large bank of stored samples
for DNA from screened Birmans and Birmans with severe heart disease.
This will allow them to proceed to the next stage of their studies,
where they will look for genetic differences in Birmans with
cardiomyopathy compared with healthy Birmans. Their hope is that by
identifying genetic differences it may be possible to produce a gene
test for cardiomyopathy in Birmans. The extended period of screening was
necessary in order to gather data in old and affected Birman cats (for
example, 41 cats ≥9 years old were screened). Considering the
age-dependent penetrance of HCM, these subpopulations of cats are of
extreme importance to better define the true cardiac phenotype/s in this
breed and to conduct more reliable genomic studies. Collecting these
valuable samples was only achievable by traveling around the UK and
targeting cats for screening from families with a history of
cardiomyopathy or old cats from relatively unaffected lines. By being so
rigorous about demanding samples from only clearly affected or clearly
unaffected cats, their genomic studies have been delayed. However,
improving the quality of the samples should improve the reliability of
the genetic testing. They are now ready to proceed with our targeted
gene testing. A 12- month no-cost extension has been requested by the
investigators to complete the project. The necessary genomic sequencing
and analysis of the samples collected will be performed during this time
period. The investigators would also like to make the following appeal: Ribonucleic acid (RNA) is a molecule that has
essential roles regulating gene expression. Examining RNA in the hearts
of normal compared with affected Birmans may be an important part of
determining the underlying genetic mutation. Since RNA is unstable, it
is essential that a storage reagent ‘RNAlater’ is used to stabilize the
RNA in tissue samples and preserve the gene expression profile.
If any cat that was scanned as affected, or
normal aged 9 or older, dies or is put to sleep for any reason, RNA from
their heart would be extremely useful. If you think that you would like
to participate in this phase of the research, if or when the time comes,
please contact the RVC research team now so that they can send RNAlater
to your veterinary practice.
By Lois Wilkie ************************ SCANNING DAY A Scanning Day has been arranged by the RVC and Birman
owners, for people unable to travel to the RVC. It is to be held at�
Mappleborough Green Village Hall, on �20th
July 2016. Mappleborough Green is just south of the M42 and handy
for the Midlands and Birmingham areas. Testing offer from our Researcher We look forward to seeing as many of you as possible in January. The Birman Heart fund was started after the Birman Cat Club Committee received letters from breeders and owners about cardiac problems in the breed. The committee contacted Veterinary Specialists who confirmed that the problem was increasing within the breed. At this time no one was raising awareness of the problem and no research was planned. The Birman committee voted to fund raise to remedy this. They have since been joined by the S & SW Birman Cat Club, the N. Birman Cat Club, and the Birman Welfare and Rescue. They have also received encouragement from the Birman BAC and the Cats Welfare Trust. Protecting breeders In order to protect breeders and the breed as a whole from unwelcome publicity the supporting clubs have concentrated on holding seminars, publishing information in the magazine, in leaflets and on their web sites. It was felt that a high profile campaign using public media would exaggerate the problem and give rise to acrimonious gossip. It could discourage sales and give the impression that the Birman Cat was less healthy than other breeds. The money raised The fund has raised over £3000 to date. Although this money is at present held in The Birman Heart Research Account, it is not Birman Cat Club money, but is held in trust on behalf of the donors until it can be handed over for research. Some of the major donors have specified that the funds go direct to a UK college, and these conditions will have to be honoured. The RVA has been mentioned, as donors are aware that research into similar problems is already being done there, and it was intimated that they would be prepared to carry out research into the Birman cat. Now that the RVA is in a position to begin research, having applied for a donation from the WINN Foundation, we are able to hand over funds to them for this research. Direct communication and steps are being taken with the RVA to do this without impacting the current WINN support or ongoing research plans. The clubs will continue to fundraise for this cause, and look forward to help from members and Birman owners. How to help our Researcher with some information Birman cats are predisposed to heart muscle disease (cardiomyopathy), which can take a range of forms: hypertrophic (HCM), where the walls of the heart are too thick; restrictive (RCM), where the walls of the heart are too stiff; dilated (DCM) where there is thinning and weakening of the heart muscle and (arrhythmogenic) right ventricular (ARVC), where the right side of the heart may be replaced by fat and scar tissue. It is currently not clear whether HCM, RCM, DCM and ARVC represent different diseases with different causes, or whether these cardiomyopathies are part of the spectrum of one disease with one genetic cause. This is a crucial question that must be answered before a genetic mutation can be identified. We have been studying Birmans with cardiomyopathy using a combination of cardiac ultrasound (echocardiography), pathology and pedigree analysis, so that we can tease out the features of these heart muscle diseases. Since the start of the study we have screened 21 cats with echocardiography and had 3 cats presented for necropsy examination and pathology. We have also received DNA samples from one cat who was screened elsewhere and died of cardiomyopathy. Pedigree analysis is underway and we have found families of Birmans with multiple members affected by more than one type of cardiomyopathy, therefore are gaining confidence that we are dealing with one disease. At the end of the July 2015 we have the opportunity to begin our first round of genetic testing, using Next-Generation Sequencing (NGS). In order to do this, we recently made an appeal for Birmans 7 years or older (ideally 10 years or older) with no family history of cardiomyopathy that do not have high blood pressure (hypertension) or an overactive thyroid gland (hyperthyroidism). These older, normal cats will form our ‘control’ group with which we will compare the DNA of cats with cardiomyopathy in the hope of finding the genetic mutation(s) responsible for cardiomyopathy in this breed. We continue to offer free of charge screening at the Queen Mother Hospital for Animals in Hertfordshire, which includes:
You can book your cat in by emailing lwilkie@rvc.ac.uk We are very grateful to everyone who has donated personally, through Breed Clubs, the Birman Heart Foundation and WINN. Without you this research would not be possible! November 2017 - A message from our researcher Dear Member We would like to ask your help to recruit new cats for the next stage of our genetic studies in Birmans. We will need to recruit ~ 45-50 cases for the 2nd arm of our genetic studies. We will use samples (DNA) from some of the cats previously recruited for the first genetic arm/stage of our project, but more samples/cats will be required. As we have done in the past, we would be more than happy to travel to local Vet practices to perform heart scans. The heart scans will be free of charge! We are specially interested in elderly cats (>9 years of age), cats showing clinical signs of cardiac disease (shortness of breath, paralysis) or cats closely related to cats affected by cardiac disease. Please could you help us with this. Please advertise our free scans? We know that people would generally be more interested in scanning young cats, but we can try to make some arrangements, such as we are happy to scan some young cats if breeders/owners would bring along some old cats or affected ones…? I look forward to hearing from you. Many thanks for your help! Best wishes |