A world of genetic research

A world of genetic research
A world of genetic research
Last Updated: March 11. 2009 1:12AM UAE / March 10. 2009 9:12PM GMT..
The death of Jett Travolta, third from left, brought the rare childhoodcondition known as Kawasaki disease to the attention of the public. APKawasakidisease, a rare autoimmune illness that mostly affects young children,was in the news recently in two different stories. In the first case,the disease was linked with Jett Travolta, son of the actor JohnTravolta. Jett died on Jan 2 after he had a seizure. He had apparentlybeen ill for some time and his parents said he had Kawasaki disease.Itbrought the condition to the attention of the public, and was followedby news of research in Australia into how the disease behaves.ProfDavid Burgner from the University of Western Australia co-led a teamthat studied the entire human genome in an attempt to find new genesinvolved in making some children more susceptible to the disease. Itwas first described by Dr Tomisaku Kawasaki in 1967, and although thecondition is treatable, little has been learnt since about its causes.Itpresents itself as an inflammatory condition. It affects several organsincluding the mucus membranes, the walls of blood vessels and lymphnodes. Its many symptoms include fever, rashes, swollen feet and hands,conjunctivitis and swollen lymph nodes. Children aged six months tofive years seem particularly susceptible. It can be fatal, but only onein 1,000 cases result in death. Although it is rare, Prof Burgnerexplained why it was important to tackle the illness.“Kawasakidisease is an important and serious illness of preschool children,” hesaid. “Importantly it is the only childhood illness that damages thecoronary arteries, in one quarter of untreated children and five to 10per cent of treated children. This coronary damage may have long-termhealth implications, including death, angina and heart attacks inchildhood and the need for coronary bypass surgery and even, rarely,heart transplant in childhood.”In the research study ProfBurgner’s team considered genetic variation among 900 cases of thedisease found in children from the US, Singapore, the Netherlands, theUK and Australia. The findings identified genes that may increase thesusceptibility of some children to the disease, but further research isneeded.“Kawasaki disease is thought to be an abnormalimmunological reaction to an unknown infectious trigger. There is astrong genetic component, so genes are important in determiningsusceptibility, as we believe all children are likely to be exposed tothe trigger,” Prof Burgner said.“Our study is the firstpublished that has investigated the entire human genome looking forimportant associated genes; most studies focus on a few candidategenes. We have identified at least eight new genes that have notpreviously been described in Kawasaki disease and some of them seem tofunction together. Some of the genes are involved in cardiovascularhealth – the function of blood vessels and in control of the immunesystem.”Identifying eight genes expands the scope of futureresearch considerably. However, studying the entire human genome is notthe biggest problem facing the researchers.“The main issue isrecruiting enough cases of Kawasaki disease, which is why we embarkedon an international study. Ideally we need up to 5,000 cases to covermore of the human genome and find more of the important genes. We werevery lucky to work with the Genome Institute of Singapore, who are oneof the top genomics facilities in the world – this made the actualgenetic laboratory work and analysis possible.”Dr BrianMcCrindle, a cardiologist from the Hospital for Sick Children inToronto, Canada, gave a talk on Kawasaki disease at the Arab HealthCongress in Dubai in January. He believes the new findings offerpotential for future research.“The research is very preliminaryand needs to be verified in other people’s work, but there are somepromising leads,” he said. “Kawasaki disease can look like otherdiseases and sometimes it doesn’t have typical presentation,” he said.Raisingawareness is vital because the disease can be misdiagnosed, butdeveloping a cure for any rare disease is difficult. However, ProfBurgner believes the identification of eight new genes will help withthe treatment process.“We hope that our work will contribute tothe development of a diagnostic test and better treatment within thenext few years, but we are not there yet,” he said.“At themoment doctors make a clinical diagnosis, based on the rash, fever etcetera, and there is no blood test that really helps. We urgently needa diagnostic test so children are treated earlier and Kawasaki diseaseis not missed, so reducing the long-term heart problems.”Findinga cure remains a possibility, though. “In Japan, for example, where onein 150 children suffer KD, it may be realistic to develop a vaccine,especially if Kawasaki disease increases the risk of atherosclerosis inlater life – this is an unknown area at present,” Prof Burgner said.Healso believes that the method used in his research of analysing theentire human genome will be adopted as the way forward in studyingother infectious diseases.“Genes are known to be important indetermining susceptibility to infection so it is a proven and excitingmethod to try and identify the important genes that make people more orless likely to get infection and once they have it, more or less likelyto survive. This should lead to better prevention and treatment. Isuspect tuberculosis, HIV, hepatitis B and C and malaria will be thelikely diseases that we will see these sorts of studies in very soon,”he said.For the moment, however, Prof Burgner is keen tocontinue to develop the research path he is pursuing with Kawasakidisease. There is also the possibility of collaborating with medicalprofessionals in the Middle East. “We are expanding thecollaborative genetics group to include Asian and other populations,aiming to work together as a scientific community to crack thismysterious disease. We would very much like to hear from anyone in yourregion who has an interest in Kawasaki disease and sees many patients,”he said.Peter Donnelly is a science correspondent for the life science division at IIR Middle East