Genotypes and phenotypes of patients with Lafora disease living in Germany.


Journal

Neurological research and practice
ISSN: 2524-3489
Titre abrégé: Neurol Res Pract
Pays: England
ID NLM: 101767802

Informations de publication

Date de publication:
2019
Historique:
entrez: 27 6 2020
pubmed: 1 1 2019
medline: 1 1 2019
Statut: ppublish

Résumé

Lafora progressive myoclonus epilepsy (Lafora disease) is a rare, usually childhood-onset, fatal neurodegenerative disease caused by biallelic mutations in The patients described in this case series initially had the suspected clinical diagnosis of Lafora disease, or unclassified progressive myoclonus epilepsy. Molecular genetic diagnostics including next generation sequencing-based diagnostic panel analysis or whole exome sequencing was performed. The parents of four out of the 11 patients are nonconsanguineous and of German origin while the other patients had consanguineous parents. Various variants were found in This is the first larger case series of Lafora patients in Germany. Our data enable an approximation of the prevalence of manifest Lafora disease in Germany to 1,69 per 10 million people. Broader application of gene panel or whole-exome diagnostics helps clarifying unclassified progressive myoclonus epilepsy and establish an early diagnosis, which will be even more important as causal therapy approaches have been developed and are soon to be tested in a phase I study.

Sections du résumé

BACKGROUND BACKGROUND
Lafora progressive myoclonus epilepsy (Lafora disease) is a rare, usually childhood-onset, fatal neurodegenerative disease caused by biallelic mutations in
METHODS METHODS
The patients described in this case series initially had the suspected clinical diagnosis of Lafora disease, or unclassified progressive myoclonus epilepsy. Molecular genetic diagnostics including next generation sequencing-based diagnostic panel analysis or whole exome sequencing was performed.
RESULTS RESULTS
The parents of four out of the 11 patients are nonconsanguineous and of German origin while the other patients had consanguineous parents. Various variants were found in
CONCLUSIONS CONCLUSIONS
This is the first larger case series of Lafora patients in Germany. Our data enable an approximation of the prevalence of manifest Lafora disease in Germany to 1,69 per 10 million people. Broader application of gene panel or whole-exome diagnostics helps clarifying unclassified progressive myoclonus epilepsy and establish an early diagnosis, which will be even more important as causal therapy approaches have been developed and are soon to be tested in a phase I study.

Identifiants

pubmed: 32587944
doi: 10.1186/s42466-019-0040-2
pmc: PMC7316188
mid: NIHMS1592569
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NINDS NIH HHS
ID : P01 NS097197
Pays : United States

Références

Front Pediatr. 2019 Jan 16;6:424
pubmed: 30701169
Epileptic Disord. 2016 Sep 1;18(S2):38-62
pubmed: 27702709
Ann Neurol. 2013 Aug;74(2):297-300
pubmed: 23913475
Brain. 1980 Jun;103(2):315-36
pubmed: 6249438
Eur J Hum Genet. 2000 Dec;8(12):946-54
pubmed: 11175283
Epilepsia. 2014 Dec;55(12):e129-33
pubmed: 25270369
Nat Genet. 1998 Oct;20(2):171-4
pubmed: 9771710
Hum Mutat. 2005 Oct;26(4):397
pubmed: 16134145
Nat Genet. 2003 Oct;35(2):125-7
pubmed: 12958597
Epilepsy Behav Case Rep. 2014 Jan 19;2:19-21
pubmed: 25667860

Auteurs

David Brenner (D)

Department of Neurology, University of Ulm, Ulm, Germany.

Tobias Baumgartner (T)

Department of Epileptology, University of Bonn Hospital, Bonn, Germany.

Sarah von Spiczak (S)

DRK-Northern German Epilepsy Center for Children and Adolescents, Schwentinental, Raisdorf, Germany.

Jan Lewerenz (J)

Department of Neurology, University of Ulm, Ulm, Germany.

Roger Weis (R)

Neuropediatric Center, Rheinhessen-Fachklinik Mainz, Mainz, Germany.

Anja Grimmer (A)

Epilepsie-Zentrum Berlin-Brandenburg, Berlin, Germany.

Petra Gaspirova (P)

Klinikum St. Marien Amberg, Amberg, Germany.

Claudia D Wurster (CD)

Department of Neurology, University of Ulm, Ulm, Germany.

Wolfram S Kunz (WS)

Department of Neurology, University of Ulm, Ulm, Germany.
Institute of Experimental Epileptology and Cognition Research, University Bonn, Bonn, Germany.

Jan Wagner (J)

Department of Neurology, University of Ulm, Ulm, Germany.

Berge A Minassian (BA)

Department of Pediatrics, University of Texas Southwestern, Dallas, USA.

Christian E Elger (CE)

Department of Epileptology, University of Bonn Hospital, Bonn, Germany.

Albert C Ludolph (AC)

Department of Neurology, University of Ulm, Ulm, Germany.

Saskia Biskup (S)

Center for Genomics and Transcriptomics (CeGaT) GmbH and Practice for Human Genetics, Tübingen, Germany.

Dennis Döcker (D)

Center for Genomics and Transcriptomics (CeGaT) GmbH and Practice for Human Genetics, Tübingen, Germany.

Classifications MeSH