Professor Steve Jeffery's research interests include: identifying the genetic basis of primary lymphoedema, study of inherited cardiac arrhythmias, investigation into the effects of drug induced arrhythmia, analysis of the genetic influences in Sudden Infant Death (SIDS) and Sudden Adult Death (SADS).
His research group's first gene discoveries were the identification of the genes for Robinow Syndrome (a rare genetic disorder characterized by short-limbed dwarfism, abnormalities in the head, face, and external genitalia, as well as vertebral segmentation) in 2000, and Noonan Syndrome, a relatively common autosomal dominant congenital disorder with associated heart defects and short stature, in 2001. Both these studies involved national and international collaborations. This work evolved into his current interests, which are understanding the genetic basis of primary lymphoedema, a long-term condition that causes swelling in the body's tissue, and cardiac arrhythmias, both of which currently receive British Heart Foundation (BHF) funding.
Professor Jeffery's researchers are the major group in the UK, and at the forefront internationally, studying the genetics of human primary lymphoedema. They have recently produced a diagnostic algorithm for this disorder, and this has allowed our group to find two genes which cause different forms of the condition, one of which is the first gene where mutations are known to produce oedema all over the body. They hope to find more genes in the next three years.
Their work on Long QT syndrome (LQTS), a disorder of the heart's electrical activity that can cause a sudden, uncontrollable, and dangerous heart rhythm, has now been ongoing for over eight years. They have set up a network to obtain families and samples from throughout the UK, in collaboration with Doctor Behr and Professor Camm in the Institute of Cardiovascular and Cell Sciences. They are investigating the known genes for mutations in high risk groups (the DARE study). The group has planned studies on Genome Wide Association for sudden infant and adult death, with colleagues including Professor Camm, Dr Elijah Behr, Dr Yalda Jamshidi and Dr Steve Bevan. They also plan to do such studies using the drug induced arrhythmia samples.
Tartaglia M, Cordeddu V, Chang H, Shaw A, Kalidas K, Crosby A, Patton MA, Sorcini M, van der Burgt I, Jeffery S, Gelb BD. . Paternal Germ-line origin and sex-ratio transmission distortion of PTPN11 mutations in Noonan Syndrome. Am J Hum. Gen. 2004 75:492-7.
Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S, Levick JR, Burnand KG, Mortimer PS; Lymphoedema Research Consortium. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation. 2007;115:1912-1920.
Connell FC, Kalidas K, Ostergaard P, Brice G, Homfray T, Roberts L, Bunyan DJ, Mitton S, Mansour S, Mortimer PS, Jeffery S. Linkage and sequence analysis indicates that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet. 2010:127;231-241.
Ostergaard P, Simpson MA, Brice G, Mansour S, Connell FC, Onoufriadis A, Child AH, Hwang J, Kalidas K, Mortimer PS, Trembath R, Jeffery S. Rapid identification of mutations in GJC2 in four limb primary lymphoedema using whole exome sequencing combined with linkage analysis. J Med Genet In Press
Behr E, Dalageorgou S, Christiansen M, Syrris P, Hughes S, Tome Esteban MT, Rowland E, Jeffery S, McKenna WJ. Sudden arrhythmic death syndrome: familial evaluation identifies heart disease in the majority of families. Eur Heart J 2008:29;1670-1680
Nolte IM, Wallace C, Newhouse SJ, Waggott D, Fu J, Soranzo N, Gwilliam R, Deloukas P, Savelieva I, Zheng D, Dalageorgou C, Farrall M, Samani NJ, Connell J, Brown M, Dominiczak A, Lathrop M, Zeggini E, Wain LV; Wellcome Trust Case Control Consortium; DCCT/EDIC Research Group, Newton-Cheh C, Eijgelsheim M, Rice K, de Bakker PI; QTGEN consortium, Pfeufer A, Sanna S, Arking DE; QTSCD consortium, Asselbergs FW, Spector TD, Carter ND, Jeffery S, Tobin M, Caulfield M, Snieder H, Paterson AD, Munroe PB, Jamshidi Y. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. PLoS One. 2009 Jul 9;4(7):e6138.
Both research programmes involve UK and international collaborations. For the lymphoedema, St George's Hospital is a tertiary referral unit, and patients come from across the UK. We are also the national gene testing sevrive for those genes known to cause primary lymphoedema. There is an active collaboration with Richard Trembath’s group at Guy’s Bioscience Centre, and with Stan Rocksn’s group in Stanford University California.
The LQT and DARE pprojects are national efforts, and we are now part of the EC funded ARITMO project looking at the genetic contribution to drug induced arrhythmia across Europe. There is a collaboration with the Serious Adverse Events Consortium (SEAC) in the USA.
British Heart Foundation