18 results on '"De Jonghe, Peter"'
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2. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy
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Syrbe, Steffen, Hedrich, Ulrike B S, Arslan, Mutluay, Serratosa, José M, Nothnagel, Michael, May, Patrick, Krause, Roland, Löffler, Heidrun, Detert, Katja, Dorn, Thomas, Vogt, Heinrich, Krämer, Günter, Riesch, Erik, Schöls, Ludger, Mullis, Primus E, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Sterbova, Katalin, Craiu, Dana C, Hoffman-Zacharska, Dorota, Korff, Christian M, Weber, Yvonne G, Steinlin, Maja, Djémié, Tania, Gallati, Sabina, Bertsche, Astrid, Bernhard, Matthias K, Merkenschlager, Andreas, Kiess, Wieland, consortium, EuroEPINOMICS RES, Gonzalez, Michael, Züchner, Stephan, Palotie, Aarno, Suls, Arvid, Müller, Stephan, De Jonghe, Peter, Helbig, Ingo, Biskup, Saskia, Wolff, Markus, Maljevic, Snezana, Schüle, Rebecca, Sisodiya, Sanjay M, Weckhuysen, Sarah, Lerche, Holger, Lemke, Johannes R, Møller, Rikke S, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande S, Depienne, Christel, Gormley, Padhraig, Guerrini, Renzo, Maher, Bridget, Hjalgrim, Helle, Jähn, Johanna, Klein, Karl Martin, Koeleman, Bobby P C, Komarek, Vladimir, LeGuern, Eric, Hernandez-Hernandez, Laura, Marini, Carla, Muhle, Hiltrud, Pal, Deb, Rosenow, Felix, Selmer, Kaja, Synofzik, Matthis, Stephani, Ulrich, Striano, Pasquale, Talvik, Tiina, von Spiczak, Sarah, Zara, Federico, and EuroEPINOMICS RES Consortium
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Adult ,Male ,Ataxia ,genetics [Epilepsy] ,genetics [Kv1.2 Potassium Channel] ,Biology ,medicine.disease_cause ,Bioinformatics ,Infantile ,Epilepsy/genetics ,Article ,Spasms ,Cohort Studies ,Epilepsy ,Young Adult ,Spasms, Infantile/genetics ,ddc:570 ,Amino Acid Sequence ,Child ,Child, Preschool ,Female ,Genetic Predisposition to Disease ,Humans ,Infant ,Kv1.2 Potassium Channel ,Pedigree ,Spasms, Infantile ,Mutation ,Genetics ,Intellectual disability ,medicine ,KCNA2 protein, human ,Preschool ,Loss function ,Kv1.2 Potassium Channel/genetics ,ddc:618 ,Genetic heterogeneity ,Seizure types ,genetics [Spasms, Infantile] ,medicine.disease ,Myoclonic epilepsy ,Human medicine ,medicine.symptom - Abstract
Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features(1-6). Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel K(V)1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of K(V)1.2-expressing neurons.
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- 2015
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3. Erratum: Corrigendum: Transcriptional regulator PRDM12 is essential for human pain perception
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Chen, Ya-Chun, primary, Auer-Grumbach, Michaela, additional, Matsukawa, Shinya, additional, Zitzelsberger, Manuela, additional, Themistocleous, Andreas C, additional, Strom, Tim M, additional, Samara, Chrysanthi, additional, Moore, Adrian W, additional, Cho, Lily Ting-Yin, additional, Young, Gareth T, additional, Weiss, Caecilia, additional, Schabhüttl, Maria, additional, Stucka, Rolf, additional, Schmid, Annina B, additional, Parman, Yesim, additional, Graul-Neumann, Luitgard, additional, Heinritz, Wolfram, additional, Passarge, Eberhard, additional, Watson, Rosemarie M, additional, Hertz, Jens Michael, additional, Moog, Ute, additional, Baumgartner, Manuela, additional, Valente, Enza Maria, additional, Pereira, Diego, additional, Restrepo, Carlos M, additional, Katona, Istvan, additional, Dusl, Marina, additional, Stendel, Claudia, additional, Wieland, Thomas, additional, Stafford, Fay, additional, Reimann, Frank, additional, von Au, Katja, additional, Finke, Christian, additional, Willems, Patrick J, additional, Nahorski, Michael S, additional, Shaikh, Samiha S, additional, Carvalho, Ofélia P, additional, Nicholas, Adeline K, additional, Karbani, Gulshan, additional, McAleer, Maeve A, additional, Cilio, Maria Roberta, additional, McHugh, John C, additional, Murphy, Sinead M, additional, Irvine, Alan D, additional, Jensen, Uffe Birk, additional, Windhager, Reinhard, additional, Weis, Joachim, additional, Bergmann, Carsten, additional, Rautenstrauss, Bernd, additional, Baets, Jonathan, additional, De Jonghe, Peter, additional, Reilly, Mary M, additional, Kropatsch, Regina, additional, Kurth, Ingo, additional, Chrast, Roman, additional, Michiue, Tatsuo, additional, Bennett, David L H, additional, Woods, C Geoffrey, additional, and Senderek, Jan, additional
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- 2015
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4. Transcriptional regulator PRDM12 is essential for human pain perception
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Chen, Ya-Chun, primary, Auer-Grumbach, Michaela, additional, Matsukawa, Shinya, additional, Zitzelsberger, Manuela, additional, Themistocleous, Andreas C, additional, Strom, Tim M, additional, Samara, Chrysanthi, additional, Moore, Adrian W, additional, Cho, Lily Ting-Yin, additional, Young, Gareth T, additional, Weiss, Caecilia, additional, Schabhüttl, Maria, additional, Stucka, Rolf, additional, Schmid, Annina B, additional, Parman, Yesim, additional, Graul-Neumann, Luitgard, additional, Heinritz, Wolfram, additional, Passarge, Eberhard, additional, Watson, Rosemarie M, additional, Hertz, Jens Michael, additional, Moog, Ute, additional, Baumgartner, Manuela, additional, Valente, Enza Maria, additional, Pereira, Diego, additional, Restrepo, Carlos M, additional, Katona, Istvan, additional, Dusl, Marina, additional, Stendel, Claudia, additional, Wieland, Thomas, additional, Stafford, Fay, additional, Reimann, Frank, additional, von Au, Katja, additional, Finke, Christian, additional, Willems, Patrick J, additional, Nahorski, Michael S, additional, Shaikh, Samiha S, additional, Carvalho, Ofélia P, additional, Nicholas, Adeline K, additional, Karbani, Gulshan, additional, McAleer, Maeve A, additional, Cilio, Maria Roberta, additional, McHugh, John C, additional, Murphy, Sinead M, additional, Irvine, Alan D, additional, Jensen, Uffe Birk, additional, Windhager, Reinhard, additional, Weis, Joachim, additional, Bergmann, Carsten, additional, Rautenstrauss, Bernd, additional, Baets, Jonathan, additional, De Jonghe, Peter, additional, Reilly, Mary M, additional, Kropatsch, Regina, additional, Kurth, Ingo, additional, Chrast, Roman, additional, Michiue, Tatsuo, additional, Bennett, David L H, additional, Woods, C Geoffrey, additional, and Senderek, Jan, additional
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- 2015
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5. A de novo gain-of-function mutation in SCN11A causes loss of pain perception
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Leipold, Enrico, primary, Liebmann, Lutz, additional, Korenke, G Christoph, additional, Heinrich, Theresa, additional, Gießelmann, Sebastian, additional, Baets, Jonathan, additional, Ebbinghaus, Matthias, additional, Goral, R Oliver, additional, Stödberg, Tommy, additional, Hennings, J Christopher, additional, Bergmann, Markus, additional, Altmüller, Janine, additional, Thiele, Holger, additional, Wetzel, Andrea, additional, Nürnberg, Peter, additional, Timmerman, Vincent, additional, De Jonghe, Peter, additional, Blum, Robert, additional, Schaible, Hans-Georg, additional, Weis, Joachim, additional, Heinemann, Stefan H, additional, Hübner, Christian A, additional, and Kurth, Ingo, additional
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- 2013
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6. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
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Lemke, Johannes R, primary, Lal, Dennis, additional, Reinthaler, Eva M, additional, Steiner, Isabelle, additional, Nothnagel, Michael, additional, Alber, Michael, additional, Geider, Kirsten, additional, Laube, Bodo, additional, Schwake, Michael, additional, Finsterwalder, Katrin, additional, Franke, Andre, additional, Schilhabel, Markus, additional, Jähn, Johanna A, additional, Muhle, Hiltrud, additional, Boor, Rainer, additional, Van Paesschen, Wim, additional, Caraballo, Roberto, additional, Fejerman, Natalio, additional, Weckhuysen, Sarah, additional, De Jonghe, Peter, additional, Larsen, Jan, additional, Møller, Rikke S, additional, Hjalgrim, Helle, additional, Addis, Laura, additional, Tang, Shan, additional, Hughes, Elaine, additional, Pal, Deb K, additional, Veri, Kadi, additional, Vaher, Ulvi, additional, Talvik, Tiina, additional, Dimova, Petia, additional, Guerrero López, Rosa, additional, Serratosa, José M, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Ruf, Susanne, additional, Wolff, Markus, additional, Buerki, Sarah, additional, Wohlrab, Gabriele, additional, Kroell, Judith, additional, Datta, Alexandre N, additional, Fiedler, Barbara, additional, Kurlemann, Gerhard, additional, Kluger, Gerhard, additional, Hahn, Andreas, additional, Haberlandt, D Edda, additional, Kutzer, Christina, additional, Sperner, Jürgen, additional, Becker, Felicitas, additional, Weber, Yvonne G, additional, Feucht, Martha, additional, Steinböck, Hannelore, additional, Neophythou, Birgit, additional, Ronen, Gabriel M, additional, Gruber-Sedlmayr, Ursula, additional, Geldner, Julia, additional, Harvey, Robert J, additional, Hoffmann, Per, additional, Herms, Stefan, additional, Altmüller, Janine, additional, Toliat, Mohammad R, additional, Thiele, Holger, additional, Nürnberg, Peter, additional, Wilhelm, Christian, additional, Stephani, Ulrich, additional, Helbig, Ingo, additional, Lerche, Holger, additional, Zimprich, Fritz, additional, Neubauer, Bernd A, additional, Biskup, Saskia, additional, and von Spiczak, Sarah, additional
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- 2013
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7. Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia
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Zimoń, Magdalena, primary, Baets, Jonathan, additional, Almeida-Souza, Leonardo, additional, De Vriendt, Els, additional, Nikodinovic, Jelena, additional, Parman, Yesim, additional, Battaloǧlu, Esra, additional, Matur, Zeliha, additional, Guergueltcheva, Velina, additional, Tournev, Ivailo, additional, Auer-Grumbach, Michaela, additional, De Rijk, Peter, additional, Petersen, Britt-Sabina, additional, Müller, Thomas, additional, Fransen, Erik, additional, Van Damme, Philip, additional, Löscher, Wolfgang N, additional, Barišić, Nina, additional, Mitrovic, Zoran, additional, Previtali, Stefano C, additional, Topaloǧlu, Haluk, additional, Bernert, Günther, additional, Beleza-Meireles, Ana, additional, Todorovic, Slobodanka, additional, Savic-Pavicevic, Dusanka, additional, Ishpekova, Boryana, additional, Lechner, Silvia, additional, Peeters, Kristien, additional, Ooms, Tinne, additional, Hahn, Angelika F, additional, Züchner, Stephan, additional, Timmerman, Vincent, additional, Van Dijck, Patrick, additional, Rasic, Vedrana Milic, additional, Janecke, Andreas R, additional, De Jonghe, Peter, additional, and Jordanova, Albena, additional
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- 2012
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8. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy
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Kurth, Ingo, primary, Pamminger, Torsten, additional, Hennings, J Christopher, additional, Soehendra, Désirée, additional, Huebner, Antje K, additional, Rotthier, Annelies, additional, Baets, Jonathan, additional, Senderek, Jan, additional, Topaloglu, Haluk, additional, Farrell, Sandra A, additional, Nürnberg, Gudrun, additional, Nürnberg, Peter, additional, De Jonghe, Peter, additional, Gal, Andreas, additional, Kaether, Christoph, additional, Timmerman, Vincent, additional, and Hübner, Christian A, additional
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- 2009
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9. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy
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Jordanova, Albena, primary, Irobi, Joy, additional, Thomas, Florian P, additional, Van Dijck, Patrick, additional, Meerschaert, Kris, additional, Dewil, Maarten, additional, Dierick, Ines, additional, Jacobs, An, additional, De Vriendt, Els, additional, Guergueltcheva, Velina, additional, Rao, Chitharanjan V, additional, Tournev, Ivailo, additional, Gondim, Francisco A A, additional, D'Hooghe, Marc, additional, Van Gerwen, Veerle, additional, Callaerts, Patrick, additional, Van Den Bosch, Ludo, additional, Timmermans, Jean-Pièrre, additional, Robberecht, Wim, additional, Gettemans, Jan, additional, Thevelein, Johan M, additional, De Jonghe, Peter, additional, Kremensky, Ivo, additional, and Timmerman, Vincent, additional
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- 2006
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10. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy
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Evgrafov, Oleg V, primary, Mersiyanova, Irena, additional, Irobi, Joy, additional, Van Den Bosch, Ludo, additional, Dierick, Ines, additional, Leung, Conrad L, additional, Schagina, Olga, additional, Verpoorten, Nathalie, additional, Van Impe, Katrien, additional, Fedotov, Valeriy, additional, Dadali, Elena, additional, Auer-Grumbach, Michaela, additional, Windpassinger, Christian, additional, Wagner, Klaus, additional, Mitrovic, Zoran, additional, Hilton-Jones, David, additional, Talbot, Kevin, additional, Martin, Jean-Jacques, additional, Vasserman, Natalia, additional, Tverskaya, Svetlana, additional, Polyakov, Alexander, additional, Liem, Ronald K H, additional, Gettemans, Jan, additional, Robberecht, Wim, additional, De Jonghe, Peter, additional, and Timmerman, Vincent, additional
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- 2004
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11. Of giant axons and curly hair
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Timmerman, Vincent, primary, De Jonghe, Peter, additional, and Van Broeckhoven, Christine, additional
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- 2000
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12. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.
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Züchner, Stephan, Noureddine, Maher, Kennerson, Marina, Verhoeven, Kristien, Claeys, Kristl, De Jonghe, Peter, Merory, John, Oliveira, Sofia A., Speer, Marcy C., Stenger, Judith E., Walizada, Gina, Danqing Zhu, Pericak-Vance, Margaret A., Nicholson, Garth, Timmerman, Vincent, and Vance, Jeffery M.
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CHARCOT-Marie-Tooth disease ,SPINAL muscular atrophy ,ALTERNATIVE medicine ,NEUTROPENIA ,AMINO acids ,GENETIC disorders - Abstract
Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of peripheral neuropathies. Different chromosomal loci have been linked with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of large GTPases and is part of the cellular fusion-fission apparatus. In transiently transfected cell lines, mutations of DNM2 substantially diminish binding of DNM2 to membranes by altering the conformation of theß3/ß4 loop of the pleckstrin homology domain. Additionally, in the Australian and Belgian pedigrees, which carry two different mutations affecting the same amino acid, Lys558, CMT cosegregated with neutropenia, which has not previously been associated with CMT neuropathies. [ABSTRACT FROM AUTHOR]
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- 2005
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13. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.
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Windpassinger, Christian, Auer-Grumbach, Michaela, Irobi, Joy, Patel, Heema, Petek, Erwin, Hörl, Gerd, Malli, Roland, Reed, Johanna A., Dierick, Ines, Verpoorten, Nathalie, Warner, Thomas T., Proukakis, Christos, Van den Bergh, Peter, Verellen, Christine, Maldergem, Lionel Van, Merlini, Luciano, De Jonghe, Peter, Timmerman, Vincent, Crosby, Andrew H., and Wagner, Klaus
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TREATMENT of spinal muscular atrophy ,NEUROPATHY ,GENETIC mutation ,GENE mapping ,ENDOPLASMIC reticulum ,HETEROZYGOSITY - Abstract
Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs. Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12-q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration. [ABSTRACT FROM AUTHOR]
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- 2004
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14. Corrigendum: Transcriptional regulator PRDM12 is essential for human pain perception.
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Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, Samara C, Moore AW, Cho LT, Young GT, Weiss C, Schabhüttl M, Stucka R, Schmid AB, Parman Y, Graul-Neumann L, Heinritz W, Passarge E, Watson RM, Hertz JM, Moog U, Baumgartner M, Valente EM, Pereira D, Restrepo CM, Katona I, Dusl M, Stendel C, Wieland T, Stafford F, Reimann F, von Au K, Finke C, Willems PJ, Nahorski MS, Shaikh SS, Carvalho OP, Nicholas AK, Karbani G, McAleer MA, Cilio MR, McHugh JC, Murphy SM, Irvine AD, Jensen UB, Windhager R, Weis J, Bergmann C, Rautenstrauss B, Baets J, De Jonghe P, Reilly MM, Kropatsch R, Kurth I, Chrast R, Michiue T, Bennett DL, Woods CG, and Senderek J
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- 2015
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15. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.
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Schubert J, Siekierska A, Langlois M, May P, Huneau C, Becker F, Muhle H, Suls A, Lemke JR, de Kovel CG, Thiele H, Konrad K, Kawalia A, Toliat MR, Sander T, Rüschendorf F, Caliebe A, Nagel I, Kohl B, Kecskés A, Jacmin M, Hardies K, Weckhuysen S, Riesch E, Dorn T, Brilstra EH, Baulac S, Møller RS, Hjalgrim H, Koeleman BP, Jurkat-Rott K, Lehman-Horn F, Roach JC, Glusman G, Hood L, Galas DJ, Martin B, de Witte PA, Biskup S, De Jonghe P, Helbig I, Balling R, Nürnberg P, Crawford AD, Esguerra CV, Weber YG, and Lerche H
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- Amino Acid Sequence, Animals, Codon, Nonsense, Cohort Studies, Comparative Genomic Hybridization, Exome, Female, Gene Deletion, Genetic Linkage, Humans, In Situ Hybridization, Fluorescence, Male, Molecular Sequence Data, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Temperature, Zebrafish, Epilepsy genetics, Mutation, Seizures, Febrile genetics, Syntaxin 1 genetics
- Abstract
Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.
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- 2014
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16. De novo mutations in HCN1 cause early infantile epileptic encephalopathy.
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Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, Cancès C, Ville D, Brilstra EH, Gobbi G, Raffo E, Bouteiller D, Marie Y, Trouillard O, Robbiano A, Keren B, Agher D, Roze E, Lesage S, Nicolas A, Brice A, Baulac M, Vogt C, El Hajj N, Schneider E, Suls A, Weckhuysen S, Gormley P, Lehesjoki AE, De Jonghe P, Helbig I, Baulac S, Zara F, Koeleman BP, Haaf T, LeGuern E, and Depienne C
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- Amino Acid Sequence, Animals, CHO Cells, Child, Preschool, Cohort Studies, Cricetinae, Cricetulus, DNA Mutational Analysis, Female, Humans, Infant, Male, Molecular Sequence Data, Mutation, Missense, Patch-Clamp Techniques, Pedigree, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Aicardi Syndrome genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels genetics, Point Mutation, Potassium Channels genetics, Spasms, Infantile genetics
- Abstract
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.
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- 2014
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17. Mutations in SEPT9 cause hereditary neuralgic amyotrophy.
- Author
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Kuhlenbäumer G, Hannibal MC, Nelis E, Schirmacher A, Verpoorten N, Meuleman J, Watts GD, De Vriendt E, Young P, Stögbauer F, Halfter H, Irobi J, Goossens D, Del-Favero J, Betz BG, Hor H, Kurlemann G, Bird TD, Airaksinen E, Mononen T, Serradell AP, Prats JM, Van Broeckhoven C, De Jonghe P, Timmerman V, Ringelstein EB, and Chance PF
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- Amino Acid Sequence, Animals, Base Sequence, Dogs, Humans, Mice, Molecular Sequence Data, Rats, Septins, Brachial Plexus Neuritis genetics, Chromosomes, Human, Pair 17 genetics, GTP Phosphohydrolases genetics, Mutation
- Abstract
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis.
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- 2005
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18. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy.
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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, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, and Timmerman V
- Subjects
- Amino Acid Sequence, Animals, COS Cells, Cell Line, Charcot-Marie-Tooth Disease metabolism, Female, Heat-Shock Proteins chemistry, Heat-Shock Proteins metabolism, Humans, Male, Molecular Chaperones, Molecular Sequence Data, Pedigree, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Sequence Homology, Amino Acid, Transfection, Charcot-Marie-Tooth Disease genetics, Heat-Shock Proteins genetics, Point Mutation, Protein Serine-Threonine Kinases
- Abstract
Distal hereditary motor neuropathies are pure motor disorders of the peripheral nervous system resulting in severe atrophy and wasting of distal limb muscles. In two pedigrees with distal hereditary motor neuropathy type II linked to chromosome 12q24.3, we identified the same mutation (K141N) in small heat-shock 22-kDa protein 8 (encoded by HSPB8; also called HSP22). We found a second mutation (K141E) in two smaller families. Both mutations target the same amino acid, which is essential to the structural and functional integrity of the small heat-shock protein alphaA-crystallin. This positively charged residue, when mutated in other small heat-shock proteins, results in various human disorders. Coimmunoprecipitation experiments showed greater binding of both HSPB8 mutants to the interacting partner HSPB1. Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders.
- Published
- 2004
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- View/download PDF
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