Expertise and current research performed: The Dept. of Medical Genetics, UMC Utrecht, is the reference centre in the field of epilepsy genetics in the Netherlands. Its research program concerns the genetic dissection of common complex diseases with polygenic or multifactorial background (epilepsy, celiac disease). Specific activities include: (1) Systematic recruitment of patient populations of interest; (2) Standardised phenotyping by a team of expert clinicians; (3) High-throughput genotyping using state-of-the-art technology; (4) Development and application of functional tests for DNA mutations; (5) Development and application of innovative biostatistical methods; (6) Guided implementation of new discoveries in clinical practice. The current research activities of the Dept. of Medical Genetics are: Delineation of epilepsy endophenotypes as proxies for genetic markers; Localisation, identification and characterisation of genes involved in: 1) idiopathic generalised epilepsy, 2) epilepsies with photosensitivity, 3) epilepsies provoked by febrile seizures; Genome-wide linkage and association studies; Bioinformatics integration of genetic studies (gene identification) and genomic studies (gene expression); Identification of functional non-coding sequence variants by combined evidence methods of association analysis.

Facilities/Equipment: The Dept. of Medical Genetics is equipped with state-of-the-art equipment for neurophysiological examinations including photosensitivity testing according to EU protocols (in collaboration with Dept. of Neurophysiology of the UMC, Utrecht and several epilepsy centres); state-of-the-art high-throughput genotyping facilities including an Illumina Beadstation and Taqman 7900 HT are also available.

Personnel involved in the project

Principal investigator: Bobby Koeleman (M). Dr., Ph.D. degree in Biomedical Sciences. Assistant professor at UMC Utrecht (tenured position), Dept. of Medical Genetics, since 2001. Postdoc at Leiden University (1995-2000), Ph.D. student at Leiden University (1991-1995). Working in the field since 1991. Research interests include: Molecular genetics & biostatistics in common complex disorders; Identification of genetic risk factors for diabetes mellitus type I; Genetics of common complex epilepsies.

Dick Lindhout (M). Prof., M.D., Ph.D. degree in medicine/medical genetics. Professor of medical genetics at Utrecht University/University Medical Centre Utrecht, since 2000. Professor of clinical genetics at Erasmus University Rotterdam (1990-2000). Working in the field since 1991. Research interests include: Genetics of common complex epilepsies and gene-environment interaction in epileptogenesis. Dorothée Kasteleijn-Nolst Trenité (F). Dr., M.D., Ph.D, M.P.H. degree in medicine and pharmacology. Assistant professor at UMC Utrecht/DMG since 2003. EU-Madame Curie Chair, La Sapienza University (Rome, 2006- ): Visual sensitivity 024224 . Senior scientist at the Epilepsy Centre of the Netherlands (1991-2001). Working in the field since1978. Research interests include: Genetics of epilepsies with photosensitivity, Reflex epilepsies, including visual sensitivity, Pharmacology and Neuropsychology of epilepsy. Dalila Pinto (F). PhD student. Ms, M.Sc., degree in medicine. Ph.D. graduation expected March 2006. Research interests include: Genetics of juvenile myoclonus epilepsy (JME) and photosensitivity. Several technicians and trial nurses of the department are involved in the genetic research of epilepsy.

Recent relevant publications/patents

1.        Pinto D, Westland B, de Haan GJ, Rudolf G, da Silva BM, Hirsch E, Lindhout D, Trenite DG, Koeleman BP. (2005) Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13. Hum Mol Genet. 14(1):171-8. 

2.        Pinto D, de Haan GJ, Janssen GA, Boezeman EH, van Erp MG, Westland B, Witte J, Bader A, Halley DJ, Kasteleijn-Nolst Trenite DG, Lindhout D, Koeleman BP (2004) Evidence for linkage between juvenile myoclonic epilepsy-related idiopathic generalized epilepsy and 6p11-12 in Dutch families. Epilepsia. 45(3):211-7. 

3.        Sander T, Schulz H, Saar K, Gennaro E, Riggio MC, Bianchi A, Zara F, Luna D, Bulteau C, Kaminska A, Ville D, Cieuta C, Picard F, Prud'homme JF, Bate L, Sundquist A, Gardiner RM, Janssen GA, de Haan GJ, Kasteleijn-Nolst-Trenite DG, Bader A, Lindhout D, Riess O, Wienker TF, Janz D, Reis A. (2000) Genome search for susceptibility loci of common idiopathic generalised epilepsies. Hum Mol Genet. 12:9(10):1465-72. 

4.        Stephani U, Tauer U, Koeleman B, Pinto D, Neubauer BA, Lindhout D. (2004) Genetics of photosensitivity (photoparoxysmal response): a review. Epilepsia 45(Suppl. 1):19-23.

5.        Serratosa JM, Gomez-Garre P, Gallardo ME, Anta B, de Bernabe DB, Lindhout D, Augustijn PB, Tassinari CA, Malafosse RM, Topcu M, Grid D, Dravet C, Berkovic SF, de Cordoba SR. (1999) A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). Hum Mol Genet 8:345-352.