Peter De Jonghe Lab

Research focus

Many neurological disorders have a genetic etiology or are complex disorders caused by an interaction between environmental and inherited factors. In our research group we focus on the clinical and molecular genetic aspects of monogenic Rare Epilepsy Syndromes (RES), Inherited Peripheral Neuropathies (IPN), Hereditary Spastic Paraplegia (HSP) or Strümpell-Lorrain disease, Hereditary Spinocerebellar and Cerebellar Ataxia (SCA and CA). The clinical, electrophysiological and neuropathological characterization of patients affected by these disorders forms the starting point for molecular genetic studies.

The mission of the Neurogenetics group is to broaden our knowledge of the genetic groundwork of RES, IPN, HSP, SCA and CA. The complexity in the field of neurogenetics grows exponentially with increasing numbers of genes and ever more unpredictable associations between genotypes and phenotypes. The direct result of our work is the description of detailed genotype-phenotype correlations that in turn drive the design of better diagnostic strategies. Our observations often provide preliminary insights into the disease mechanisms and help to select specific mutations for additional functional studies that might contribute to the design of therapeutic strategies.

The research in our group is strongly driven by the clinical substrate of these disorders. It is at the level of the patients and their families that the scientific question arises and is in the end also answered, at least under the form of a genetic diagnosis and ultimately hopefully as a treatment. Through systematic patient sampling at the Antwerp University Hospital, other centers in Belgium and in fact through extensive international collaborations we established one of the largest collections of DNA samples and clinical data of IPN and RES patients and families in the world.

We conduct genetic studies in the lab using a wide range of molecular techniques. These include classical genetic approaches, such as linkage analysis and homozygosity mapping in nuclear families or patient cohorts. In addition to classic Sanger sequencing we now heavily rely on next-generation sequencing techniques, most notable whole-exome-sequencing e.g. in patient-parents trios and NGS panels in cohorts of patients. These technologies have now evolved into robust and price-efficient workhorses that allow experiments that were inconceivable a few years ago. This has revolutionized our way of thinking in molecular genetics.

In the epilepsy project, we demonstrated that de novo mutations in the sodium-channel gene SCN1A are the major cause of severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome), a devastating form of childhood epilepsy. We reported that dominant mutations in GLUT1, representing the main glucose transporter in the human brain, can cause Paroxysmal Exercise-induced Dyskinesia (PED) and early-onset absence epilepsy, thus expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for these clinical syndromes. Via patient-parent trio sequencing we showed that de novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic encephalopathy. Mutations in KCNQ2 were already known to be associated with benign familial neonatal convulsions but we discovered that many KCNQ2 mutations result in a severe epileptic encephalopathy. We mapped novel loci for GEFS+, temporal lobe epilepsy and temporal-occipital lobe epilepsy with migraine. In the domain of IPN we now concentrate on the pure
motor (distal Hereditary Motor Neuropathies or dHMN) and pure sensory neuropathies (Hereditary Sensory Neuropathies or HSN). We recently contributed to the identification of HINT1 as a major gene for automosomal recessive dHMN with neuromyotonia. In HSN we contributed to the identification of SCN11A, ATL1, KIF1A and FAM134B as causal genes We performed extensive genotype-phenotype correlations in families with known and novel mutations in DNM2, TRPV4 and INF2. We reported the largest comprehensive study of the molecular architecture of IPNs starting in the first year of life. We identified mutations in the mitochondrial DNA polymerase gamma (POLG) gene as the major cause of PEO. Our latest contribution to HSP consist of the identification of GBA2 as the gene involved in a complex form of HSP. We also demonstrated that mutations in SACSIN are common in patients with a late onset triad of peripheral neuropathy, spasticity and cerebellar ataxia. All our research topics projects are strongly embedded in international collaborations. We are curating the Inherited Peripheral Neuropathies Mutation Database for the European CMT consortium and are part of the FP7-funded NEUROMICS network. We are heading, together with the group of Prof. Ingo Helbig the EuroEPINOMICS consortium on Rare Epilepsy Syndromes (RES) in the framework of an European Science Foundation (ESF) EUROCORES network. In the HSP/SCA project we have extensive collaborations with Prof. S. Züchner, John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine.

Publications

Transcriptional regulator PRDM12 is essential for human pain perceptionChen Y* Auer-Grumbach M* Matsukawa S Zitzelsberger M Themistocleous A Strom T Samara C Moore A Cho L Young G Weiss C Schabhuttl M Stucka R Schmid A Parman Y Graul-Neumann L Heinritz W Passarge E Watson R Hertz J Moog U Baumgartner M Valente E Pereira D Restrepo C Katona I Dusl M Stendel C Wieland T Stafford F Reimann F Von Au K Finke C Willems P Nahorski M Shaikh S Carvalho O Nicholas A Karbani G Mcaleer M Cilio M Mchugh J Murphy S Irvine A Jensen U Windhager R Weis J Bergmann C Rautenstrauss B Baets J De Jonghe P Reilly M Kropatsch R Kurth I Chrast R Michiue T Bennett D Woods C Senderek JNATURE GENETICS, 47, 803-8, 2015* These authors contributed equally
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikesLemke J, Lal D, Reinthaler E, Steiner I, Nothnagel M, Alber M, Geider K, Laube B, Schwake M, Finsterwalder K, Franke A, Schilhabel M, Jähn J, Muhle H, Boor R, Van Paesschen W, Caraballo R, Fejerman N, Weckhuysen S, De Jonghe P, Larsen J, Moller R, Hjalgrim H, Addis L, Tang S, Hughes E, Pal D, Veri K, Vaher U, Talvik T, Dimova P, Guerrero López R, Serratosa J, Linnankivi T, Lehesjoki A, Ruf S, Wolff M, Buerki S, Wohlrab G, Kroell J, Datta A, Fiedler B, Kurlemann G, Kluger G, Hahn A, Haberlandt D, Kutzer C, Sperner J, Becker F, Weber Y, Feucht M, Steinböck H, Neophythou B, Ronen G, Gruber-Sedlmayr U, Geldner J, Harvey R, Hoffmann P, Herms S, Altmüller J, Toliat M, Thiele H, Nurnberg P, Wilhelm C, Stephani U, Helbig I, Lerche H, Zimprich F, Neubauer B, Biskup S, Von Spiczak SNATURE GENETICS, 45, 1067-72, 2013
A de novo gain-of-function mutation in SCN11A causes loss of pain perceptionLeipold E, Liebmann L, Korenke G, Heinrich T, Giesselmann S, Baets J, Ebbinghaus M, Goral R, Stödberg T, Hennings J, Bergmann M, Altmüller J, Thiele H, Wetzel A, Nürnberg P, Timmerman V, De Jonghe P, Blum R, Schaible H, Weis J, Heinemann S, Hübner C, Kurth INATURE GENETICS, 45, 1399-404, 2013
KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathyWeckhuysen S, Mandelstam S, Suls A, Audenaert D, Deconinck T, Claes G, Deprez L, Smets K, Hristova D, Yordanova I, Jordanova A, Ceulemans B, Jansen A, Hasaerts D, Roelens F, Lagae L, Yendle S, Stanley T, Heron S, Mulley J, Berkovic S, Scheffer I, De Jonghe PANNALS OF NEUROLOGY, 71, 15-25, 2012
Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathiesZimón M, Baets J, Auer-Grumbach M, Berciano J, Garcia A, Lopez-Laso E, Merlini L, Hilton-Jones D, Mcentagart M, Crosby A, Barisic N, Boltshauser E, Shaw C, Landouré G, Ludlow C, Gaudet R, Houlden H, Reilly m, Fischbeck K, Sumner C, Timmerman V, Jordanova A, De Jonghe PBRAIN, 133, 1798-809, 2010

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News

New genes identified with key role in the development of severe childhood epilepsies

25/09/2014 - An international team of researchers, including scientists from VIB and Antwerp University identified novel causes for severe childhood epilepsies.

New technology for the detection of genetic abnormalities which lead to serious epilepsy

22/01/2014 - An international consortium including researchers from VIB, the University of Antwerp and KU Leuven demonstrates that defects in the CHD2 gene lead to Dravet Syndrome, a serious form of epilepsy.

Researchers studying hereditary illnesses of peripheral nervous system make important discovery

10/09/2012 - Antwerp researchers (VIB/University of Antwerp) were the first to discover that mutations in the HINT1 gene are linked to a specific type of peripheral neuropathy.

Fruit fly steps in to fight human disease

22/06/2009 - VIB scientists have successfully introduced genes coding for a variant of the Charcot-Marie-Tooth (CMT) disease, into fruit flies.

Defect in gene causes 'Neuralgic Amyotrophy'

25/09/2005 - Researchers from VIB connected to the University of Antwerp, have uncovered a small piece of the molecular puzzle of this disease by identifying the defects in the gene responsible for this disorder.

Peter De Jonghe

Peter De Jonghe

Research area(s)

Bio

​​M.D.: Univ. of Antwerp, Antwerp, Belgium, 1978
Neurologist: Univ. of Antwerp, Antwerp, Belgium, 1983
PhD: Univ. of Antwerp, Antwerp, Belgium, 1998
VIB Group leader since 1999
Associate Professor, Univ. of Antwerp since 2002
Professor, Univ. of Antwerp since 2008

Contact Info

VIB-UAntwerp Center for Molecular NeurologyGebouw VCampus Drie EikenUniversiteitsplein 1 2610 ANTWERPENRoute description