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Epilepsie und geistige Entwicklungsstörung

​​​​The focus of our working group is the elucidation of genetic causes and pathomechanisms of intellectual disability and neurodevelopmental disorders (NDD) with and without epilepsy. Intellectual disability affects approx. 2 percent of the population, and the overwhelming majority is due to genetic variants. Modern diagnostics, including karyotyping, array analysis, gene panel and exome sequencing yield diagnoses in more than half of the cases. Still, the underlying causes of the remainder remain unknown. We perform whole exome sequencing (often of parent-offspring trios or affected siblings) of individuals with NDD. Definite diagnoses are reported back to the referring physicians. Findings in still not described, but potential NDD genes (so called candidate genes, see our full list (E​xcel; PDF)) are followed on by a detailed clinical phenotyping, recruiting further comparable cases or joining ongoing international efforts, and eventually by functional analyses to prove pathogenicity and/or understand the underlying pathomechanisms.​

Ansprechpartner

Prof. Dr. Johannes Lemke

Telefon: 0341 97 – 23800
E-Mail: johannes.lemke@uniklinik-leipzig.de
Fokus auf Epilepsie
Publikationen

Prof. Dr. Rami Jamra
Telefon: 0341 97 – 23803
E-Mail: rami.aboujamra@medizin.uni-leipzig.de
Fokus auf NDD
Publikationen​​

Team

  • Rami Jamra (Google Scholar)
  • Chiara Klöckner
  • Ilona Krey
  • Diana-Gabriela Le Duc
  • Johannes Lemke
  • Johann Lieberwirth
  • Johannes Luppe
  • Bernt Popp
  • ​Konrad Platzer (Google ScholarTwitter)
  • ​Meret Wegler

Ehemalige Mitglieder:

  • Benjamin Büttner​
  • Anja Finck
  • Susanne Horn​
  • Sonja Martin​

Aktuelle Projekte

  1. ​​​Exome sequencing to identify novel epilepsy and NDD genes. The project is ongoing since 4 years and we have described or contributed to description over 20 novel NDD disorders (see our publications list)
  2. Transcriptome sequencing (using RNA of blood) in order to indirectly identify variants that cannot be captured by exome sequencing, and to develop working hypothesis on pathomechanisms.
  3. Systematic scoring of candidate genes in order to prioritize our candidate genes (Ex​cel; PDF). We are now developing the score to be web-based and valid for a broader spectrum of phenotypes. If you find an overlap with our list of genes, do not hesitate to contact us to collaborate on that.

Publikationen

  • Pathogenic WDFY3 variants cause neurodevelopmental disorders and opposing effects on brain size.
    Le Duc D, Giulivi C, Hiatt SM, Napoli E, Panoutsopoulos A, Harlan De Crescenzo A, Kotzaeridou U, Syrbe S, Anagnostou E, Azage M, Bend R, Begtrup A, Brown NJ, Büttner B, Cho MT, Cooper GM, Doering JH, Dubourg C, Everman DB, Hildebrand MS, Santos FJR, Kellam B, Keller-Ramey J, Lemke JR, Liu S, Niyazov D, Payne K, Person R, Quélin C, Schnur RE, Smith BT, Strober J, Walker S, Wallis M, Walsh L, Yang S, Yuen RKC, Ziegler A, Sticht H, Pride MC, Orosco L, Martínez-Cerdeño V, Silverman JL, Crawley JN, Scherer SW, Zarbalis KS, Jamra R. Brain. 2019 Sep 1;142(9):2617-2630. doi: 10.1093/brain/awz198. PMID:31327001
  • Identification of a Loss-of-Function Mutation in the Context of Glutaminase Deficiency and Neonatal Epileptic Encephalopathy.
    Rumping L, Büttner B, Maier O, Rehmann H, Lequin M, Schlump JU, Schmitt B, Schiebergen-Bronkhorst B, Prinsen HCMT, Losa M, Fingerhut R, Lemke JR, Zwartkruis FJT, Houwen RHJ, Jans JJM, Verhoeven-Duif NM2, van Hasselt PM, Jamra R. JAMA Neurol. 2019 Mar 1;76(3):342-350. doi: 10.1001/jamaneurol.2018.2941. PMID:30575854
  • GRIN2A-related disorders: genotype and functional consequence predict phenotype.
    Strehlow V, Heyne HO, Vlaskamp DRM, Marwick KFM, Rudolf G, de Bellescize J, Biskup S, Brilstra EH, Brouwer OF, Callenbach PMC, Hentschel J, Hirsch E, Kind PC, Mignot C, Platzer K, Rump P, Skehel PA, Wyllie DJA, Hardingham GE, van Ravenswaaij-Arts CMA, Lesca G, Lemke JR1; GRIN2A study group. Brain. 2019 Jan 1;142(1):80-92. doi: 10.1093/brain/awy304. PMID:30544257
  • De novo variants in neurodevelopmental disorders with epilepsy.
    Heyne HO, Singh T, Stamberger H, Abou Jamra R, Caglayan H, Craiu D, De Jonghe P, Guerrini R, Helbig KL, Koeleman BPC, Kosmicki JA, Linnankivi T, May P, Muhle H, Møller RS, Neubauer BA, Palotie A, Pendziwiat M, Striano P, Tang S, Wu S; EuroEPINOMICS RES Consortium, Poduri A, Weber YG, Weckhuysen S, Sisodiya SM, Daly MJ, Helbig I, Lal D, Lemke JR.
    Nat Genet. 2018 Jul;50(7):1048-1053. doi: 10.1038/s41588-018-0143-7. Epub 2018 Jun 25. PMID:29942082
  • De novo variants in PAK1 lead to intellectual disability with macrocephaly and seizures.
    Horn S, Au M, Basel-Salmon L, Bayrak-Toydemir P, Chapin A, Cohen L, Elting MW, Graham JM, Gonzaga-Jauregui C, Konen O, Holzer M, Lemke J, Miller CE, Rey LK, Wolf NI, Weiss MM, Waisfisz Q, Mirzaa GM, Wieczorek D, Sticht H, Abou Jamra R. Brain. 2019 Nov 1;142(11):3351-3359. doi: 10.1093/brain/awz264. PMID:31504246​
Philipp-Rosenthal-Str. 55, Haus W
04103 Leipzig
Telefon:
0341 - 97 23840 (Sprechstunde)
Sekretariat:
0341 - 97 23800
Fax:
0341 - 97 23819
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