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  1. 1. netics genetics genetics genetics genetics genetics genetics genetics genetics genetics cs genetics genetics genetics genetics genetics genetics genetics genetics ge genetics genetics genetics genetics genetics genetics genetics genetics gene netics genetics genetics genetics genetics genetics genetics genetics genetics cs genetics genetics genetics genetics genetics genetics genetics genetics ge genetics genetics genetics genetics genetics genetics genetics genetics gene Genetics, Carrier Testing, Tests during Pregnancy and for Newborn Babies genetics Cystic Fibrosis Trust. Registered Charity No. 1079049. Registered Company No. 3880213.
  2. 2. geneticscontents INTRODUCTION.....................................................1 SCREENING..................................................................5 WHAT IS CYSTIC FIBROSIS?............................2 Newborn screening ........................................................5 What are your chances of being a carrier? ...........5 WHAT ARE GENES? ...............................................3 How are carrier tests performed? ............................5 Why is a baby born with CF?....................................3-4 Who should be offered carrier testing?..................6 SUMMARY: .....................................................................6 This booklet is not intended to replace genetic counselling by a specialist. It is designed to help you when you consult your Introduction General Practitioner (GP) or speak People who have Cystic Fibrosis (CF) were born to the counsellors at your regional genetic centre (see pages 11-13). with it and, unless a cure for the condition is found, will have it for the rest of their lives. Cystic Fibrosis is inherited; it can’t be caught after birth. Published by Cystic Fibrosis Trust This booklet is aimed at explaining the inheritance May 2002 process and why some babies are born with Reprinted August 2004 and August 2005 Cystic Fibrosis. © Cystic Fibrosis Trust 2002.This booklet may be copied in whole or in part During the past ten years, there have been without prior permission being sought from the copyright holders, provided the exciting advances in our knowledge of Cystic purpose of copying is not for commercial Fibrosis. This booklet will explain: gain and provided due acknowledgement How CF is inherited. is given. What is known about the CF gene. How carriers of the CF gene can be identified. How you might avoid having a child with Cystic Fibrosis. What we mean by gene therapy. 1
  3. 3. PREGNANCY ..............................................................7 THE CYSTIC FIBROSIS GENE..........................9 What is antenatal diagnosis? ........................................7 Are there different types of faulty What does antenatal diagnosis involve?..................7 CF genes? ............................................................................9 When should I see a genetic counsellor? ...........7-8 Gene therapy - what is it, and will it Pre-implantation genetic diagnosis ............................8 be a cure? ........................................................................10 SUMMARY .........................................................................8 REGIONAL GENETICS CENTRES .....11-13 What is Cystic Fibrosis? Cystic Fibrosis is the UK’s People with Cystic Fibrosis face a daily regimen of treatment. This includes physiotherapy to most common life-threatening help clear the mucus from the lungs, antibiotics inherited disease affecting to fight infection, and enzyme supplements around 7,500 children and with food to help digestion. Although new adults. treatments are being developed, which will undoubtedly improve the quality and length of People with CF produce very thick sticky life for people with CF, the condition remains mucus that clogs their lungs and digestive serious. There is no cure at present, but gene systems making it difficult to breathe and therapy to cure the lung disease is a realistic absorb food properly. Serious symptoms possibility within the foreseeable future. and complications of CF include infection and inflammation of the lungs, malnutrition, Cystic Fibrosis is an inherited or genetic diabetes, liver problems and osteoporosis. disease.This means that the condition occurs because of a faulty gene, in this case carried When CF was first recognised as a disease and passed on by both parents who do not in the 1930s most babies with CF were themselves have Cystic Fibrosis. The condition only expected to live a few months; in the is caused by a single faulty gene (called the 1960s life expectancy had reached early Cystic Fibrosis Transmembrane Conductance teens. At present, over half those affected Regulator - or CFTR gene). A person must genetics can expect to live beyond the age of 30 inherit two copies of this faulty gene - one and with earlier diagnosis and modern from each parent - to develop Cystic Fibrosis. treatment, life expectancy and quality of life will continue to improve. 2
  4. 4. What are Genes? Genes carry the blueprint for producing What we look like - and how Why is a baby our bodies work - are controlled by our genes. born with CF? We all have different genes and A baby is born with Cystic When there is a faulty CF gene that’s why we are all different. Fibrosis only if both its parents in both the sperm and the egg at The word genetic simply means are carriers of the defective CF conception the result is a baby ‘to do with genes’. And genetic gene. Even then, though both who will have CF regardless of research - the study of genes - parents each carries one faulty whether it is a boy or a girl. is a branch of science that is gene will not mean that the baby helping us understand more will be born with CF for certain. The diagram shows the risk for and more about what happens When both parents are carriers each pregnancy for a couple who inside our bodies and how we it is a matter of chance whether are both carriers of the faulty can inherit genetic characteristics a particular sperm or a particular CF gene. from our parents. The section egg contains the faulty gene or a in the next column Why is a healthy one. baby born with CF? - will help you understand more about why and how babies can be born with the inherited disease Cystic Fibrosis. We all have thousands of genes. Genes carry the blueprint for producing proteins that allow our bodies to function properly. The gene for CF happens to be one of them. Our genes come in pairs, with one of each inherited from each parent. A person with CF has two faulty CF genes in each cell of the body while the parents each have one faulty If both parents are carriers, a child has: gene and one that works normally. Parents of children with A one in four chance of being born with CF. CF are therefore called “CF A two in four chance of being a carrier. This child will be perfectly carriers”. Since their healthy healthy but may pass the faulty gene onto its own children. gene allows normal functioning, A one in four chance of being perfectly normal and having no being a carrier does not mean faulty CF gene to pass on to future generations. they have Cystic Fibrosis. 3
  5. 5. proteins that allow our bodies to function properly. Two carrier parents might have Occasionally carriers have been several affected children, or only found to have some symptoms in unaffected children - or, indeed, a common with CF, such as mixture of both affected and persistent chest infections or If unaffected children. It’s only sterility in men due to blocked or only possible to calculate the chances; absent sperm ducts. However, one parent it’s impossible to predict what most carriers not only are has the faulty gene, there’s no will happen for any particular perfectly healthy, they may have a cause for concern. A baby must baby before conception. health advantage (such as inherit a defective gene from If a couple already have a child protection from diseases such as both parents to be born with with CF this doesn’t change the cholera) over non-carriers, which Cystic Fibrosis. risks in the next pregnancy. Each would explain why the faulty pregnancy has exactly the same No-one is to blame for genetic gene is so common. chance (1 in 4) of resulting in a diseases. We all have some child with Cystic Fibrosis. Most people find out they are genes that don’t work properly, carriers when: but we’re not usually aware of it All this means that CF is a genetic a) they have a child with CF, because there’s also a normal disease. Most carriers of the or gene that takes over. defective gene have no idea that b) a close relative is affected they’re carriers, because they’re and they’re tested. usually completely healthy. QUICK FACTS In the UK, one person in 25 is a carrier The organs that are most severely and one in every 2,500 babies will have affected are the lungs and the pancreas, Cystic Fibrosis - that means that there’s a resulting in breathing problems and poor genetics baby born with CF nearly every day. digestion. Liver disease occurs in some people and diabetes is increasingly common in later life. Infertility is a particular problem in men with Cystic Fibrosis. 4
  6. 6. Screening People can be tested to see whether they carry the CF Gene. We hope that from 2006 all newborn babies in the UK will be tested to see whether they have Cystic Fibrosis. Adults can be tested to see whether they are carriers of the CF gene, and if their partner is also tested and also found to be a carrier, they can make informed choices about the implications of being parents. Newborn This is part of the “Guthrie test”, Regional Genetics Centre listed which involves taking a drop of on pages 11-13; talk to your GP screening blood from the heel of the baby about getting referred to your Until recently, only 20% of babies that is tested for a number of local Centre or contact them born in the UK were tested different conditions. Most babies directly. It is up to each routinely for CF in the newborn will get a clean bill of health, but individual whether they wish to period. The remaining 80% of for those few found to have CF, be tested or not. babies were not tested and only they will gain hugely from getting diagnosed after the onset of The table below outlines the the proper treatment straight chest, bowel or other symptoms chance of being a carrier if you away and serious lung damage and signs of Cystic Fibrosis. are related to someone with can be avoided or delayed. Often CF would go undiagnosed Cystic Fibrosis: for months if not years. What are your Brother or sister 2 in 3 The Government announced in chances of being a Aunt or uncle 1 in 2 2001 that it would be carrier? First cousin 1 in 4 introducing newborn screening Second cousin 1 in 8 For most people in the UK, for all babies carried out within Third cousin 1 in 16 where there is no family history the first week of life. of Cystic Fibrosis, the chance of being a carrier is 1 in 25. If you How are carrier have a child with CF, then both tests performed? parents must be carriers (the Tests for checking whether only exception is when one someone is carrying the faulty CF parent has CF and their partner gene are done usually using a is a carrier). simple blood or mouthwash test. For relatives of a person with CF With the mouthwash test you the chance of being a carrier is simply swill a weak sugar and salt higher than the general solution around your mouth for population. Tests are now 20 seconds. Cells from this available for relatives and their solution are then used for genetic partners to check whether or testing. Most types of faulty CF not they are carriers. These are genes (but not all) can be available on the NHS from your detected using this test. 5
  7. 7. Who should be Several successful trials of population carrier screening have offered carrier been carried out, although there testing? isn’t yet agreement about Relatives of those known to have whether such general screening SUMMARY CF have a higher chance of being should be part of NHS care. At a carrier and can be tested along the moment, you’re likely to with their partners at Regional encounter screening only when Genetic Centres (see pages 11- it’s part of an extended research It is possible to detect CF 13 for contact details). Whenever trial or if you’re known to be carriers in any family where a carrier is detected, carrier tests there’s already an affected at risk. child available for testing.This are then made available to their If you want to be tested, then means that brothers and relatives - hence the term sisters of people with CF - “cascade” screening. you should contact the Genetics and sometimes more distant Centre for your region (listed at relatives like aunts, uncles, It is theoretically possible to test the end of this booklet). nieces and nephews - can be everybody to find out who are Different Centres may vary in tested. carriers, but unless you’re related their attitude to testing non- to someone with CF this test is relatives of CF families and some Current tests can detect up not routinely available on the to 90% of CF carriers in the Centres prefer you to be NHS. Because the CF gene is so general population. referred to them by your GP. However, a negative isn’t common, it makes sense to test Since 1991 all pregnant women absolutely definitive, even for its presence in the whole attending the Edinburgh antenatal though the risk of being a population, particularly amongst carrier is reduced from people who are thinking of having clinics have been offered couple about 1 in 25 to less than a baby. Carrying out CF testing screening early in pregnancy. If the 1 in 200. would identify carrier couples mother is found to be a CF before they have children. carrier her partner is tested. If From 2002/3 all newborn both are carriers, antenatal babies in the UK will soon This would allow them to avoid counselling is given and they are be tested to see whether having children with CF, or to offered antenatal diagnosis. they have Cystic Fibrosis. monitor the pregnancy with This will allow them to antenatal diagnosis (see Cystic Fibrosis carrier testing is receive proper treatment page 11-13). available privately and the CF straight away. Trust may be contacted for details. 6
  8. 8. Pregnancy Carrier couples have many options to consider before undertaking When both parents are carriers of the faulty CF gene they have a 1 in 4 chance of having a baby with CF with every pregnancy (see page 3 Why is a baby born with CF). While there have been great improvements in the length and quality of life for people with CF, it still remains a serious condition and carrier couples should think very seriously before undertaking a pregnancy. There are a number of options pregnancy is an option for you to However, it must be kept in mind open to couples: some opt for consider. It’s wise to have that there’s a very small chance “taking a chance” and hope that thought carefully about this (1-2%) that a miscarriage might the baby will not have CF and before going ahead with an occur as a result of the some choose not to have any antenatal diagnosis test. The test procedure. (more) children. Many choose to is not generally recommended have an antenatal test that will for those who find termination Occasionally, antenatal diagnosis tell them whether the pregnancy unacceptable, although some is carried out later, between 15- will result in a baby being born parents would prefer to know in 18 weeks of pregnancy, using with Cystic Fibrosis. order to be better prepared. ‘amniocentesis’ to get a sample of cells from the foetus. Recently, alternatives to antenatal Amniocentesis is an outpatient testing are emerging that ensure What does procedure and, although it’s even that an embryo does not carry antenatal diagnosis less likely to cause miscarriage the faulty CF gene before it is involve? than chorionic villus biopsy implanted (see page 8 for an (1 in 100), it’s often avoided The test is usually carried out explanation about pre-implantation because most women think that between 10-15 weeks of genetic diagnosis). Other options if a termination is necessary it pregnancy, although it can be include artificial insemination using should be done as early performed a little later in some donor sperm, or egg donation as possible. Centres - usually using chorionic fertilised with the father’s sperm, villus sampling (CVS) sometimes which is then implanted in the mother’s womb. known as chorionic villus biopsy When should I see (CVB). It involves staying in a genetic hospital for a few hours. A small What is antenatal sample of the placenta is removed counsellor? The CF Trust recommends that diagnosis? and sent to the laboratory for anyone considering antenatal analysis. The results are compared This is a procedure that screening should see a genetic with those of the parents or any determines early on in the counsellor before going through other child with CF in the family. pregnancy whether or not a with the procedure. Genetic If the tissue from the foetus has baby will have Cystic Fibrosis. counselling offers the two faulty CF genes, then the If the baby is found to be opportunity to explore and child will have CF. The test unaffected, you’ll be reassured to discuss the options available as results take a few days to come go ahead with the pregnancy. If well as any other genetic aspects through and the parents are told tests show that the unborn child of Cystic Fibrosis. as quickly as possible. does have CF, terminating the 7
  9. 9. a pregnancy. Genetic counselling is offered A genetic counsellor will help both before and during a guide people through the pregnancy. If taken before a necessary procedures in the pregnancy, this allows a more rapidly changing field of diagnosis cool headed appraisal of the but ultimately it is the parents’ options and decision making. decision. Most antenatal diagnosis so far Centres has been carried out for couples Pre-implantation where it is who already have had one child genetic diagnosis available. Centres with Cystic Fibrosis. These Another way for couples who offering pre-implantation genetic families have a clear idea of what are both carriers to have a baby diagnosis are listed on page 13. it’s like to have a child with CF known to be free of CF is by The mother has to take fertility and may have made up their pre-implantation genetic diagnosis. hormones to ripen a number of own minds which option they The procedure involves in vitro her eggs and these have to be would like to take. fertilisation (IVF) similar to the collected through a fine tube technique used for infertile passed into her lower abdomen. As time goes on, more and more Generally two healthy embryos couples. Embryos are created in couples who are both carriers are put into the mother’s womb. a “test tube” from the mother’s will be identified and will have no The chance of a successful eggs and the father’s sperm. The experience of the disease; it will pregnancy is 25%, and there is a embryos are then tested for CF be harder for them to decide higher risk of having twins. and only embryos free of CF are what to do. Counselling will help implanted in the mother’s womb. There are only a few centres in anyone who wants to discuss the question of antenatal testing and, This is not an easy option, nor is the UK where pre-implantation whatever decision, people will be it freely available. It can be time- genetic diagnosis is offered. It is supported. consuming and disruptive to the also costly, at around £3,000 for family routine as it usually each attempt and not all health requires travel to one of the few authorities are prepared to pay for the treatment. SUMMARY genetics Always consult a specialist and a Antenatal diagnosis is usually Lower risk pregnancies aren’t genetic counsellor before recommended for couples who usually tested for Cystic Fibrosis. deciding for or against antenatal are both carriers and have a 1 in Pregnant mothers who would diagnosis. Ideally, you should 4 risk of having an affected child. like a test should discuss this consider this before pregnancy For most of these couples, with their GP or obstetrician. has started. antenatal diagnosis is possible using a relatively simple test between 10 and 12 weeks of pregnancy. 8
  10. 10. The Cystic Fibrosis Gene Every one of us Every one of us has about 30,000 genes. In 1989 an international team of scientists identified the CF gene. They found that it makes a protein called CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), which carries salt in and out of the cells that line the lungs and digestive system. In people with CF, the CFTR doesn’t work properly. Usually, it gives out too much chloride (salt) and not enough water. This helps to explain why the secretions of the airways are sticky and become easily infected and why the sweat of a person with CF is excessively salty. Are there different A negative test is not absolutely These people usually have a definite, although the risk of rarer mutation for at least one of types of faulty CF being a carrier is markedly their genes. One of the better genes? reduced. known of these rarer genes is There are many different ways in called R117H. Since two faulty CF genes are which genes can be faulty. inherited, one from each parent, Different mutations make Variations of a gene are called a child with CF may inherit the different faults in the CFTR “mutations”. Over 1,000 different same mutation or different ones protein. Some faults mean that mutations of the CF gene have - dependant upon what mutation CFTR isn’t present at all, others been discovered, but most the parents are carrying. Does result in CFTR being present, but people in the UK have exactly the type of mutation make a either not working very well, or the same gene defect.This difference to the severity of the not enough of it is produced.The common mutation is called condition or to the type of variations in the severity of ΔF508 (pronounced delta F508) symptoms that people with CF symptoms experienced by and 75% of people with CF in experience? people with CF can be partly the UK carry two ΔF508 genes. explained by the types of their The vast majority (94%) of There is little difference between CF gene mutations. people with CF has this mutation those who have two ΔF508 as, at least, one of their faulty CF genes or one ΔF508 gene along Information about the many genes. While there are a large with another faulty gene. In different mutations and their number of CF gene mutations, nearly all of these cases, the effects on the function of CFTR there are only 20 or so common pancreas is unable to release the is important as it may lead to ones. enzymes needed for proper new treatments for CF tailor- digestion of food and they will made to help CFTR function Cystic Fibrosis carrier tests look have to take enzymes as pills better.These future treatments for these more common with their food. could be used on their own or in mutations, and therefore picks up combination with gene therapy most, but not all, CF carriers. Only 5% of people with CF have (see page 10 Gene therapy). sufficient pancreatic function to digest their food properly. 9
  11. 11. has about 30.000 genes, a fault in one of them causes Cystic Fibrosis. It is important to remember that One exciting prospect is gene CF genes are not the whole therapy.This means getting story. Other factors can influence normal genes into the cells of the outcome and quality of life of patients who have only defective people with Cystic Fibrosis.These CF genes. It sounds simple and include getting both early logical but there are many treatment and the proper difficulties. Discovering the best management advised at Specialist way to achieve this is an of a CF Centres. Genetic factors enormous undertaking and it huge other than the CF gene itself can must be said that progress won’t programme of also play a role.These are called be instant. Gene therapy is such research further trials funded by modifier genes and researchers a novel form of treatment that the CF Trust are now in hand. are just beginning to identify we must proceed cautiously. The story of CF treatment must them and discover their role in The first approaches are to try be put into perspective. Only a Cystic Fibrosis. and get normal genes into the few years ago, the outlook for a lungs of people with CF, because baby born with CF was, to say Gene therapy - it’s in the lungs that the most the least, grim.Today, young what is it, and will damage occurs. adults with CF are living into it be a cure? Clinical trials have already shown their twenties, thirties and even Many people - particularly those that gene therapy works in forties - and these people are with a child who has CF - want principle, but for it to be an living active fulfiling lives. to know whether research will effective treatment many The quality and length of life lead to a cure. obstacles need to be overcome. should be even greater as a Before the gene was identified, While normal genes were taken result of the new genetics.The treatment was like a game of up into the cells, they did not new research techniques, which chance. Each symptom was work very effectively nor for very have been and are currently, treated as it appeared.There was long. Researchers are now supported by the CF Trust, and no way of getting to the focussing their efforts on applied so tentatively over ten underlying cause of the disease. developing new methods of years ago, are now bearing fruit. Now that the gene has been more effectively delivering the Further advice is available from found, and the function of the genes into the cells where they the Cystic Fibrosis Trust - full CFTR protein is beginning to be are needed and enabling them to contact details are shown on understood, scientists are trying produce functioning CFTR.The the back cover of this booklet. several new approaches. results from early clinical trials are encouraging and as a result The future is an optimistic one. 10
  12. 12. Notes CF Trust Helpline 0845 859 1000 For information, advice and support (including the contents of this booklet).
  13. 13. South East Trent Department of Clinical Dept of Clinical Genetics Genetics The Leicester Royal The Churchill Hospital Infirmary NHS Trust Old Road LEICESTER OXFORD OX3 7LJ LE1 5WW 01865 226066 0116 258 5736 Wessex Clinical Genetics North Trent Clinical Service Genetics Service Princess Anne Hospital Sheffield Children’s Hospital Northern Ireland Coxford Road Western Bank N Ireland Regional Genetics SOUTHAMPTON SHEFFIELD S10 2TH Service SO16 5YA 0114 271 7025 Department Medical Genetics 023 807 96166 Nottingham Clinical Floor A Genetics Service Belfast City Hospital South West 2nd Floor H Block Lisburn Road Peninsula Clinical Genetics City Hospital NHS Trust BELFAST BT9 7AB Service Hucknall Road 02890 329241 Ext. 2364 Dept of Clinical Genetics NOTTINGHAM NG5 1PB Royal Devon & Exeter 0115 962 7728 Hospital Barrack Road West Midlands EXETER EX2 5DW West Midlands Regional 01392 403151 Genetics Centre Clinical Genetics Service Clinical Genetics Level B Birmingham Women’s Regional St Michael’s Hospital Hospital Genetics genetics Southwell Street Edgbaston Centres BRISTOL BS2 8EG BIRMINGHAM B15 2TG continued 0117 928 5652 0121 627 2630 overleaf 12
  14. 14. Regional Genetics Centres - continued Scotland Genetics Nurse UCH Birnie Unit University College London North Scotland Highland Acute Hospitals 25 Grafton Way Regional Genetics Service NHS Trust LONDON Medical School Raigmore Hospital WC1E 6DB Foresterhill INVERNESS IV2 3UJ 020 7679 9300 ABERDEEN AB9 2ZD 01463 704000 01224 552882 Wolfson Family Clinic Hammersmith Hospital Dundee - Department of Wales Du Cane Road Human Genetics Medical Genetics Services LONDON Pathology Department for Wales W12 0HS Ninewells Hospital Institute of Medical Genetics 020 8383 8168 DUNDEE DD1 9SY University Hospital of Wales 01382 632035 Heath Park Leeds General Infirmary CARDIFF CF14 4XW Clarendon Wing South East Scotland Regional 029 2074 4028 Belmont Grove Genetics Centre LEEDS Dept of Clinical Genetics Western General Hospital Pre-Implantation LS2 9NS Crewe Road Genetic Diagnosis 0113 392 6908 EDINBURGH EH4 2XU Clinics 0131 651 1012 Guy’s & St Thomas’ Hospital Centre for PGD West of Scotland Regional 4th Floor Genetics Service Thomas Guy House The Clinical Genetics Centre Guy’s Hospital Yorkhill Hospitals St Thomas Street GLASGOW G3 8SJ LONDON 0141 201 0808 SE1 9RT 020 7955 4429 13 List updated January 2004
  15. 15. Notes CF Trust Helpline 0845 859 1000 For information, advice and support (including the contents of this booklet).
  16. 16. genetics s genetics genetics genetics genetics genetics genetics genetics genetics gen netics genetics genetics genetics genetics genetics genetics genetics genetic etics genetics genetics genetics genetics genetics genetics genetics genetics s genetics genetics genetics genetics genetics genetics genetics genetics gen netics genetics genetics genetics genetics genetics genetics genetics genetic etics genetics genetics genetics genetics genetics genetics genetics genetics For further general information and literature published by the CF Trust, please contact: Cystic Fibrosis Trust 11 London Road Bromley Kent BR1 1BY Tel: 020 8464 7211 Fax: 020 8313 0472 E-mail: enquiries@cftrust.org.uk www.cftrust.org.uk GEN0805