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Vincent Timmerman
Peripheral Neuropathy
VIB Department of Molecular Genetics, University of Antwerp
PhD: Univ. of Antwerp, Antwerp, Belgium, '93
VIB Group leader since 1999
Associate Professor, Univ. of Antwerp since 2002 |
e-mail
phone +32 3 820 24 99
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Current team members
Group leader: Vincent Timmerman
Staff scientists: Joy Irobi, Sophie Janssens
Postdoctoral scientist: Katrien Janssens
Ph.D. Students: Anne Holmgren, Annelies Rotthier, Biljana Ermanoska, Elke Ydens, Leonardo De Almeida Souza, Ricardo Gonçalves
Support personnel: Bob Asselbergh, Kim Van Hoof, Sofie Goethals, Tinne Ooms, Vicky De Winter
Keywords
peripheral neuropathy - gene mapping and cloning - haplotyping - gene expression profiling - neuronal cell biology
Science
Inherited peripheral neuropathies belong to the most common neuromuscular disorders and occur worldwide (1/2500). The best known is Charcot-Marie-Tooth disease (CMT), an inherited disorder first described in 1886. Most patients have a progressive weakness and wasting of foot and hand muscles. Sometimes patients need walking aids or become wheelchair dependent even at a young age. The clinical variability and genetic heterogeneity often poses difficult diagnostic problems. Treatment is currently supportive (braces and foot surgery) and a therapy that fundamentally alters the course of these diseases is still lacking. A better understanding of the molecular architecture of the peripheral nerve, the functional pathways, the myelination process and the complex interaction between the axon, the myelinating Schwann cells and muscle is crucial to identify targets for therapeutic interventions. The identification of loci, genes and disease-causing mutations involved in the inherited peripheral neuropathies is the first step in this understanding. Over the years, we have assembled a unique collection of unrelated pedigrees, clinical data and DNA samples. Genotype/phenotype correlations are made using clinical, neurophysiological and neuropathological data provided by clinicians and pathologists. The molecular genetic methods used in our laboratory include: genome-wide searches and genetic linkage analyses in extended families, identification of novel genes using DNA cloning techniques, gene prediction, mutation analysis of candidate genes and functional analysis of some of the genes. Our research group has been successful in the identification and confirmation of several genes and mutations responsible for various types of inherited peripheral neuropathies. Everything started with the identification of the CMT1A duplication as the most frequent mutation in CMT neuropathies. And in the past 5 years we were able to identify 7 loci through genome-wide linkage studies and we identified 5 novel genes: ARHGEF10, RAB7, HSP22, SEPT9 and YARS. In addition, we contributed to the identification of 7 other genes through international collaboration (HSP27, MFN2, DNM2, BSCL2, SETX, SH3TC2 and FGD4). Although many genes still need to be identified, we have initiated functional studies in selected genes in order to understand the pathomechanism of mutations, the biology of myelination and axonal transport, and the differential gene expression in motor and sensory neurons. The current focus is to gain knowledge on distal hereditary motor neuropathies (distal HMN), hereditary sensory and autonomic neuropathies (HSAN) and intermediate types of CMT.
Press releases
See also press release (22/06/2009): Fruit fly steps in to fight human disease - based on a publication in PNAS (Erik Storkebaum et al., Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy)
Selected Publications
Storkebaum E, Leitão-Goncalves R, Godenschwege T, Nangle L, Mejia M, Bosmans I, Ooms T, Jacobs A, Van Dijck P, Yang X, Schimmel P, Norga K, Timmerman V, Callaerts P, Jordanova A
Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy
P NATL ACAD SCI USA 106, 11782-7, 2009
Kurth I, Pamminger T, Hennings J, Soehendra D, Huebner A, Rotthier A, Baets J, Senderek J, Topaloglu H, Farrell S, Nürnberg G, Nürnberg P, De Jonghe P, Gal A, Kaether C, Timmerman V, Hübner C
Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy
NAT GENET 41, 1179-81, 2009
Jordanova A, Irobi J, Thomas F, Van Dijck P, Meerschaert K, Dewil M, Dierick I, Jacobs A, De Vriendt E, Guergueltcheva V, Rao C, Tournev I, Gondim F, D'Hooghe M, Van Gerwen V, Callaerts P, Van Den Bosch L, Timmermans J, Robberecht W, Gettemans J, Thevelein J, De Jonghe P, Kremensky I, Timmerman V
Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy
NAT GENET 38, 197-202, 2006
Kuhlenbäumer G, Hannibal c, Nelis E, Schirmacher A, Verpoorten N, Meuleman J, Watts d, De Vriendt E, Young P, Stogbauer F, Halfter H, Irobi J, Goossens D, Del-Favero J, Betz g, Hor H, Kurlemann G, Bird d, Airaksinen E, Mononen T, Serradell p, Prats m, Van Broeckhoven C, De Jonghe P, Timmerman V, Ringelstein B, Chance f
Mutations in SEPT9 cause hereditary neuralgic amyotrophy
NAT GENET 37, 1044-1046, 2005
Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V
Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy
NAT GENET 36, 597-601, 2004
Search Publications
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