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Publications

Syrbe S*, Hedrich UB*, Riesch E*, Djémié T*, Müller S, Møller RS, Maher B, Hernandez-Hernandez L, Synofzik M, Caglayan HS, Arslan M, Serratosa JM, Nothnagel M, May P, Krause R, Löffler H, Detert K, Dorn T, Vogt H, Krämer G, Schöls L, Mullis PE, Linnankivi T, Lehesjoki AE, Sterbova K, Craiu DC, Hoffman-Zacharska D, Korff CM, Weber YG, Steinlin M, Gallati S, Bertsche A, Bernhard MK, Merkenschlager A, Kiess W; EuroEPINOMICS RES, Gonzalez M, Züchner S, Palotie A, Suls A, De Jonghe P, Helbig I, Biskup S, Wolff M, Maljevic S, Schüle R, Sisodiya SM, Weckhuysen S, Lerche H, Lemke JR. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat Genet. 2015 Apr;47(4):393-9. doi: 10.1038/ng.3239. Epub 2015 Mar 9. PubMed PMID: 25751627. * contributed equally.
The publication of Ulrike Hedrich of Prof. Lerche's group has been voted „Paper of the month“ by Research4Rare in February 2015. An Abstract in english and german can be found here. Congratulations!

Pressrelease of the DGN (German)
Pressrelease of the Hertie-Institute for clinical Brain Research (German)

Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, Joensuu T, Canafoglia L, Franceschetti S, Michelucci R, Markkinen S, Heron SE, Hildebrand MS, Andermann E, Andermann F, Gambardella A, Tinuper P, Licchetta L, Scheffer IE, Criscuolo C, Filla A, Ferlazzo E, Ahmad J, Ahmad A, Baykan B, Said E, Topcu M, Riguzzi P, King MD, Ozkara C, Andrade DM, Engelsen BA, Crespel A, Lindenau M, Lohmann E, Saletti V, Massano J, Privitera M, Espay AJ, Kauffmann B, Duchowny M,  Møller RS, Straussberg R, Afawi Z, Ben-Zeev B, Samocha KE, Daly MJ, Petrou S, Lerche H, Palotie A, Lehesjoki AE. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet 2015;47:39-46.  doi: 10.1038/ng.3144. Epub 2014 Nov 17. PubMed PMID: 25401298

Shaikh RS, Reuter P, Sisk RA, Kausar T, Shahzad M, Maqsood MI, Yousif A, Ali M, Riazuddin S, Wissinger B, Ahmed ZM (2015) Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy. Eur J Hum Genet. 2015 Apr;23(4):473-80. doi: 10.1038/ejhg.2014.136. Epub 2014 Jul 23. PubMed PMID: 25052312.

Groome JR, Lehmann-Horn F, Fan C, Wolf M, Winston V, Merlini L, Jurkat-Rott K. NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery. Brain. 2014 Apr;137(Pt 4):998-1008. doi: 10.1093/brain/awu015. Epub 2014 Feb 18. PubMed PMID: 24549961

Lemke JR, Hendrickx R, Geider K, Laube B, Schwake M, Harvey RJ, James VM, Pepler A, Steiner I, Hörtnagel K, Neidhardt J, Ruf S, Wolff M, Bartholdi D, Caraballo R, Platzer K, Suls A, De Jonghe P, Biskup S, Weckhuysen S. GRIN2B mutations in west syndrome and intellectual disability with focal epilepsy. Ann Neurol. 2014 Jan;75(1):147-54. doi: 10.1002/ana.24073. PubMed PMID: 24272827.

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; EuroEPINOMICS RES Consortium, 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, Lerche H. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nature Genetics 2014. doi: 10.1038/ng.3130. [Epub ahead of print].
The publication of Julian Schubert of Prof. Lerche's group has been voted "Paper of the Month" by Research4Rare. An abstract in english and german can be found here. Congratulations!

Shared Pressrelease of the DGN & DGfE (German)

BMBF-Newsletter Gesundheitsforschung, Ausgabe Februar 2014: Vorstellung von IonNeurONet

Ionenkanalerkrankungen sind das Schwerpunktthema der Dezember-Ausgabe der Zeitschrift Medizinische Genetik. An den 10 Übersichtartikeln, in denen typische Ionenkanalerkrankungen einzelner Organsysteme vorgestellt werden, waren alle wissenschaftlichen IonNeurONet Partner beteiligt. In einem weiteren Artikel wurde außerdem das IonNeurONet Projekt kurz dargestellt.  Eine Übersicht zu allen veröffentlichten Artikeln findet sich hier

  • Kubisch C. Schwerpunkt Ionenkanalerkrankungen. medgen 2013 25: 425-426. doi: 10.1007/s11825-013-0414-8.
  • Maljevic S, Hedrich UBS, Lerche H. Ionenkanalerkrankungen des Gehirns – monogene Epilepsien. medgen 2013 25: 431-439. doi: 10.1007/s11825-013-0425-5.
  • Borck G, Kubisch C. Ausgewählte Ionenkanalerkrankungen des peripheren Nervensystems. medgen 2013 25: 448-453. doi: 10.1007/s11825-013-0418-4.
  • Lehmann-Horn F, Jurkat-Rott K. Monogene Ionenkanalerkrankungen der Skelettmuskulatur. medgen 2013 25: 454-461. doi: 10.1007/s11825-013-0419-3.
  • Reuter P, Kohl S, Bernd A, Wissinger B. Erbliche Ionenkanalerkrankungen der Netzhaut. medgen 2013 25: 469-474. doi: 10.1007/s11825-013-0422-8.
  • Zurek B, Graessner H, Lerche H, IonNeurONet Konsortium, IonNeurONet – Deutsches Netzwerk für neurologische und ophthalmologische Ionenkanalerkrankungen. medgen 2013 25: 501–505. doi: 10.1007/s11825-013-0427-3.

Orhan G, Bock M, Schepers D, Ilina EI, Reichel SN, Löffler H, Jezutkovic N, Weckhuysen S, Mandelstam S, Suls A, Danker T, Guenther E, Scheffer IE, Jonghe PD, Lerche H, Maljevic S. Dominant-negative Effects of KCNQ2 Mutations are Associated with Epileptic Encephalopathy. Ann Neurol. 2013 Dec 7. doi: 10.1002/ana.24080. [Epub ahead of print]

Fan C, Lehmann-Horn F, Weber MA, Bednarz M, Groome JR, Jonsson MK, Jurkat-Rott K. Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Cav1.1 mutation. Brain. 2013 Nov 15. [Epub ahead of print] PubMed PMID: 24240197.
The publications of Chunxiang Fan of PD Dr. Jurkat-Rott's group has been voted "Paper of the Month" by Research4Rare. An abstract in english and german can be found here. Congratulations!

Yang R, Jurkat-Rott K, Cao J, Wang G, Seelig HP, Yang C, Liu G, Pan L, Zheng H, Lehmann-Horn F. Hypokalemic periodic paralysis induced by thymic hyperplasia and relieved by thymectomy. JAMA Neurol. 2013 Nov 1;70(11):1436-9. doi: 10.1001/jamaneurol.2013.3918. PubMed PMID: 24061198.

Charles G, Zheng C, Lehmann-Horn F, Jurkat-Rott K, Levitt J. Characterization of hyperkalemic periodic paralysis: a survey of genetically diagnosed individuals. J Neurol. 2013 Oct;260(10):2606-13. doi: 10.1007/s00415-013-7025-9. Epub 2013 Jul 25. PubMed PMID: 23884711; PubMed Central PMID: 23884711.

Sánchez-Albisua I, Schöning M, Jurkat-Rott K, Lerche H. Possible effect of corticoids on hemiplegic attacks in severe hemiplegic migraine. Pediatr Neurol. 2013 Oct;49(4):286-8. doi: 10.1016/j.pediatrneurol.2013.04.011. Epub 2013 Jul 4. PubMed PMID: 23831250.

Lemke JR, Lal D, Reinthaler EM, Steiner I, Nothnagel M, Alber M, Geider K, Laube B, Schwake M, Finsterwalder K, Franke A, Schilhabel M, Jähn JA, Muhle H, Boor R, Van Paesschen W, Caraballo R, Fejerman N, Weckhuysen S, De Jonghe P, Larsen J, Møller RS, Hjalgrim H, Addis L, Tang S, Hughes E, Pal DK, Veri K, Vaher U, Talvik T, Dimova P, López RG, Serratosa JM, Linnankivi T, Lehesjoki AE, Ruf S, Wolff M, Buerki S, Wohlrab G, Kroell J, Datta AN, Fiedler B, Kurlemann G, Kluger G, Hahn A, Haberlandt DE, Kutzer C, Sperner J, Becker F, Weber YG, Feucht M, Steinböck H, Neophythou B, Ronen GM, Gruber-Sedlmayr U, Geldner J, Harvey RJ, Hoffmann P, Herms S, Altmüller J, Toliat MR, Thiele H, Nürnberg P, Wilhelm C, Stephani U, Helbig I, Lerche H, Zimprich F, Neubauer BA, Biskup S, von Spiczak S. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013 Aug 11. doi: 10.1038/ng.2728. [Epub ahead of print] Pressemitteilung

Cavel-Greant D, Lehmann-Horn F, Jurkat-Rott K. The impact of permanent muscle weakness on quality of life in periodic paralysis: a survey of 66 patients. Acta Myol. 2012 Oct;31(2):126-33.

Fauler M, Jurkat-Rott K, Lehmann-Horn F. Membrane excitability and excitation-contraction uncoupling in muscle fatigue. Neuromuscul Disord. 2012 Dec;22 Suppl 3:S162-7.

Jurkat-Rott K, Groome J, Lehmann-Horn F. Pathophysiological role of omega pore current in channelopathies. Front Pharmacol. 2012;3:article 112, 1-19.

Seebohm G, Strutz-Seebohm N, Ursu ON, Preisig-Müller R, Zuzarte M, Hill EV, Kienitz MC, Bendahhou S, Fauler M, Tapken D, Decher N, Collins A, Jurkat-Rott K, Steinmeyer K, Lehmann-Horn F, Daut J, Tavar JM, Pott L, Bloch W, Lang F. Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome. FASEB J. 2012 Feb;26(2):513-22.

Lemke JR, Riesch E, Scheurenbrand T, Schubach M, Wilhelm C, Steiner I, Hansen J, Courage C, Gallati S, Bürki S, Strozzi S, Simonetti BG, Grunt S, Steinlin M, Alber M, Wolff M, Klopstock T, Prott EC, Lorenz R, Spaich C, Rona S, Lakshminarasimhan M, Kröll J, Dorn T, Krämer G, Synofzik M, Becker F, Weber YG, Lerche H, Böhm D, Biskup S. Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia 2012; 53:1387-98.

Füll Y, Seebohm G, Lerche H, Maljevic S. A conserved threonine in the S1-S2 loop of K(V)7.2 and K(V) 7.3 channels regulates voltage-dependent activation. Pflugers Arch. 2012 Dec 28. [Epub ahead of print]

Diagnostic-Panels Ion Channel Disorders

In approximately 80-90% of clinically diagnosed complex genetic diseases the causative gene variation is not found. This is due to the fact that the classical sequencing of gene by gene is excessively expensive and very time consuming. Diagnostic Panels enable us to sequence all genes associated with a certain disease simultaneously.

In collaboration with CeGaT GmbH, the clinical partners have developed nine diagnostic-panels for ion channel disorders including 114 genes:

CACNA1A, CACNB4, KCNA1, KCNC3, KCNJ10, SCN8A

Panel 1: Episodic ataxia

 

ATP1A2, ATP1A3, CACNA1A, KCNK18, SCN1A, SLC2A1

Panel 2: Migraine

 

ACTA1, ANO5, ATP2A1, CACNA1S, CAV3, CCDC78, CLCN1, COL6A1, COL6A2, COL6A3, DYSF, DMD, GLRA1, GLRB, HSPG2, KCNA1, KCNJ2, KCNJ18, KCNQ2, RYR1, SCN4A, SEPN1, TPM3, TTN

Panel 3: Myotonias, periodic paralyses, MH-disposition & core myopathy:

 

AGRN, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COLQ, DOK7, GFPT1, LAMB2, MUSK, PLEC, RAPSN, SCN4A

Panel 4: Congenital myasthenic syndrome (CMS):

 

CABP4, CACNA1F, CACNA2D4, CNGA1, CNGA3, CNGB1, CNGB3, KCNJ13, KCNV2, TRPM1

Panel 5: Ionen channel disorders in inherited retinopathies:

 

NTRK1, SCN9A, TRPA1, TRPM8, TRPV1, WNK1

Panel 6: Hereditary neuropathic pain syndrome:

 

KCNMA1, MR1, NOL3, P2RX7, PRRT2, SLC2A1

Panel 7: Paroxysmal movment disorders:

 

AKAP9, ANK2, CACNA1C, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A, SNTA1

Panel 8: Long QT-syndrome:

 

ATP6B1, BSND, CA2, CASR, CLCNKA, CLCNKB, CLDN16, CLDN16, CLDN19, FXYD2, HSD11B2, KCNJ1, KCNJ10, KLHL3, NR3C2, SCNN1A, SCNN1B, SCNN1G, SLC12A1, SLC12A2, SLC12A3, SLC12A5, SLC12A7, SLC4A1, SLC4A4, SLC4A5, WNK1, WNK4

Panel 9: Bartter-syndrome:

 

For further information on Diagnostic Panels Ion Channel Disorders and the Order Form for Diagnostic Panels click here

In the area of Epilepsy & Metabolic Disorders CeGaT has already developed 16 panels for simultaneous analysis of up to 361 genes associated with epilepsy, migraine and metabolic disorders.