Peter De Jonghe
Neurogenetics
VIB Department of Molecular Genetics, University of Antwerp

MD: Univ. of Antwerp, Antwerp, Belgium, '78 Neurologist: Univ. of Antwerp, Antwerp, Belgium, '83 PhD: Univ. of Antwerp, Antwerp, Belgium, '98 VIB Group leader since 1999 Associate Professor, Univ. of Antwerp since 2002 Professor Univ. of Antwerp since 2008

e-mail phone +32 3 265 10 50 ADDRESS

Current team members
Group leader: Peter De Jonghe
Project leader: Albena Jordanova
Staff scientist: Gert Van Goethem
Postdoctoral scientists: Arvid Suls, Sarah Weckhuysen
Ph.D. Students: Jonathan Baets, Kristien Peeters, Magdalena Zimon, Philip Holmgren
Support personnel: Ann Löfgren, Ann Vandenbroucke, Els De Vriendt, Iris Smouts, Jolien De Ryck, Tine Deconinck, Tine Van Dyck

Keywords
peripheral neuropathy - epilepsy - progressive external ophthalmoplegia - spastic paraplegias - gene mapping and cloning

Science

Many neurodegenerative 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 genetic aspects of inherited peripheral neuropathies and inherited epilepsy syndromes. The clinical, electrophysiological and neuropathological characterization of patients affected by these disorders forms the starting point for molecular genetic studies. Classical genetic approaches, like linkage analysis and homozygosity mapping are performed in extended pedigrees or cohorts of nuclear inbred families, resulting in the mapping of genetic loci and the identification of novel genes. Based on genotype-phenotype studies in homogeneous patient-populations we delineate the range of clinical variables. These observations often provide preliminary insights in the disease mechanisms and help to select specific mutations for additional functional studies. These findings also help to develop algorithms for diagnostic DNA analysis in these disorders and provide rationale for therapeutic interventions.
Our main research topics are the molecular genetics of peripheral neuropathies, idiopathic epilepsy syndromes, progressive external ophthalmoplegia (PEO) and spastic paraplegias. 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 the GLUT1, representing the main glucose transported 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. We identified mutations in GABRG2 and SCN1B in families with generalized epilepsy and febrile seizures plus (GEFS+) and mutations in KCNQ2 in benign familial neonatal convulsions. We mapped novel loci for GEFS+, temporal lobe epilepsy and temporal-occipital lobe epilepsy with migraine. We identified mutations in the ATP1A2 gene in families with migraine and epilepsy. We performed extensive genotype-phenotype correlations in families with known and novel mutations in the dynamin 2 gene, causing Dominant Intermediate Charcot-Marie-Tooth disease type B (DI-CMTB). We identified mutations in the mitochondrial DNA polymerase gamma (POLG) gene as the major cause of PEO. We described additional mutations in Spastin , the gene involved in SPG4 and made genotype-phenotype correlations in a large group of patients with SPG3a. In addition we host a molecular diagnostic unit that provides DNA diagnoses and performs research on neurological diseases, and we are curating the Inherited Peripheral Neuropathies Mutation Database
(http://www.molgen.ua.ac.be/CMTMutations/) for the European CMT consortium.
Our current focus is on mapping additional loci for inherited peripheral neuropathies and inherited epilepsy syndromes and to identify the genes in the newly mapped loci.

Press releases
See also press release (22/06/2009): Fruit fly steps in to fight human disease based on a publication in leading journal Proceedings of the National Academy of Sciences (Erik Storkebaum et al.)

Zimón 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 P
Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies
BRAIN 133, 1798-809, 2010



Claeys K, Züchner S, Kennerson M, Berciano J, Garcia A, Verhoeven K, Storey E, Merory J, Bienfait H, Lammens M, Nelis E, Baets J, De Vriendt E, Berneman Z, De Veuster I, Vance J, Nicholson G, Timmerman V, De Jonghe P
Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy
BRAIN 132, 1741-52, 2009



Ivanova N, Claeys K, Deconinck T, Litvinenko I, Jordanova A, Auer-Grumbach M, Haberlova J, Lofgren A, Smeyers G, Nelis E, Mercelis R, Plecko B, Priller J, Zamecnik J, Ceulemans B, Erichsen A, Bjorck E, Nicholson G, Sereda M, Seeman P, Kremensky I, Mitev V, De Jonghe P
Hereditary Spastic Paraplegia 3A Associated With Axonal Neuropathy
ARCH NEUROL-CHICAGO 64, 706-13, 2007



Deprez L, Peeters K, Van Paesschen W, Claeys K, Claes G, Suls A, Audenaert D, Van Dyck T, Goossens D, Del-Favero J, De Jonghe P
Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to chromosome 9q
NEUROLOGY 68, 1995-2002, 2007



Claes G, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P
De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy
AM J HUM GENET 68, 1327- 1332, 2001

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