Hallmann, Kerstin, Zsurka, Gabor ORCID: 0000-0002-6379-849X, Moskau-Hartmann, Susanna, Kirschner, Janbernd ORCID: 0000-0003-1618-7386, Korinthenberg, Rudolf ORCID: 0000-0002-4638-3460, Ruppert, Ann-Kathrin, Ozdemir, Ozkan, Weber, Yvonne, Becker, Felicitas, Lerche, Holger, Elger, Christian E., Thiele, Holger, Nuernberg, Peter, Sander, Thomas and Kunz, Wolfram S. ORCID: 0000-0003-1113-3493 (2014). A homozygous splice-site mutation in CARS2 is associated with progressive myoclonic epilepsy. Neurology, 83 (23). S. 2183 - 2188. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

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Abstract

Objective: We report a consanguineous family with 2 affected individuals whose clinical symptoms closely resembled MERRF (myoclonus epilepsy with ragged red fibers) syndrome including severe myoclonic epilepsy, progressive spastic tetraparesis, progressive impairment of vision and hearing, as well as progressive cognitive decline. Methods: After excluding the presence of pathogenic mitochondrial DNA mutations, whole-exome sequencing of blood DNA from the index patient was performed. Detected homozygous mutations and their cosegregation were confirmed by Sanger sequencing. CARS2 (cysteinyl-tRNA synthetase 2, mitochondrial) messenger RNA analysis was performed by reverse transcription PCR and sequencing. Results: We identified a homozygous c.655G>A mutation in the CARS2 gene cosegregating in the family. The mutation is localized at the last nucleotide of exon 6 and thus is predicted to cause aberrant splicing. Analysis of the CARS2 messenger RNA showed that the presence of the mutation resulted in removal of exon 6. This leads to an in-frame deletion of 28 amino acids in a conserved sequence motif of the protein involved in stabilization of the acceptor end hairpin of tRNA(Cys). Conclusion: CARS2 is a novel disease gene associated with a severe progressive myoclonic epilepsy most resembling MERRF syndrome.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hallmann, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zsurka, GaborUNSPECIFIEDorcid.org/0000-0002-6379-849XUNSPECIFIED
Moskau-Hartmann, SusannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirschner, JanberndUNSPECIFIEDorcid.org/0000-0003-1618-7386UNSPECIFIED
Korinthenberg, RudolfUNSPECIFIEDorcid.org/0000-0002-4638-3460UNSPECIFIED
Ruppert, Ann-KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozdemir, OzkanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, FelicitasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lerche, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elger, Christian E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunz, Wolfram S.UNSPECIFIEDorcid.org/0000-0003-1113-3493UNSPECIFIED
URN: urn:nbn:de:hbz:38-420967
DOI: 10.1212/WNL.0000000000001055
Journal or Publication Title: Neurology
Volume: 83
Number: 23
Page Range: S. 2183 - 2188
Date: 2014
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1526-632X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSFER-RNA SYNTHETASE; DISEASE; GENEMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42096

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