Universität zu Köln

Doss, Sarah, Lohmann, Katja, Seibler, Philip, Arns, Bjoern, Klopstock, Thomas, Zuehlke, Christine, Freimann, Karen, Winkler, Susen, Lohnau, Thora, Drungowski, Mario, Nuernberg, Peter, Wiegers, Karin, Lohmann, Ebba, Naz, Sadaf ORCID: 0000-0002-1912-0235, Kasten, Meike, Bohner, Georg ORCID: 0000-0002-1919-092X, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Endres, Matthias and Klein, Christine (2014). Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation. J. Neurol., 261 (1). S. 207 - 213. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-1459

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Abstract

DYTCA is a syndrome that is characterized by predominant dystonia and mild cerebellar ataxia. We examined two affected siblings with healthy, consanguineous, Turkish parents. Both patients presented with a combination of childhood-onset cerebellar ataxia, dystonia, and sensory axonal neuropathy. In the brother, dystonic features were most pronounced in the legs, while his sister developed torticollis. Routine diagnostic investigations excluded known genetic causes. Biochemical analyses revealed a mitochondrial respiratory chain complex IV and a coenzyme Q10 deficiency in a muscle biopsy. By exome sequencing, we identified a homozygous missense mutation (c.154A>C; p.Thr52Pro) in both patients in exon 2 of the COX20 (FAM36A) gene, which encodes a complex IV assembly factor. This variant was confirmed by Sanger sequencing, was heterozygous in both parents, and was absent from 427 healthy controls. The exact same mutation was recently reported in a patient with ataxia andmuscle hypotonia. Among 128 early-onset dystonia and/ or ataxia patients, we did not detect any other patient with a COX20 mutation. cDNA sequencing and semi-quantitative analysis were performed in fibroblasts from one of our homozygous mutation carriers and six controls. In addition to the exchange of an amino acid, the mutation led to a shift in splicing. In conclusion, we extend the phenotypic spectrumof a recently identified mutation in COX20 to a recessively inherited, early-onset dystonia-ataxia syndrome that is characterized by reduced complex IV activity. Further, we confirm a pathogenic role of this mutation in cerebellar ataxia, but this mutation seems to be a rather rare cause.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Doss, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohmann, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Seibler, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Arns, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Klopstock, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuehlke, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Freimann, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Susen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohnau, Thora UNSPECIFIED UNSPECIFIED UNSPECIFIED Drungowski, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiegers, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohmann, Ebba UNSPECIFIED UNSPECIFIED UNSPECIFIED Naz, Sadaf UNSPECIFIED orcid.org/0000-0002-1912-0235 UNSPECIFIED Kasten, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Bohner, Georg UNSPECIFIED orcid.org/0000-0002-1919-092X UNSPECIFIED Ramirez, Alfredo UNSPECIFIED orcid.org/0000-0003-4991-763X UNSPECIFIED Endres, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-452455
DOI:	10.1007/s00415-013-7177-7
Journal or Publication Title:	J. Neurol.
Volume:	261
Number:	1
Page Range:	S. 207 - 213
Date:	2014
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1432-1459
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CEREBELLAR-ATAXIA; CERVICAL DYSTONIA Multiple languages Clinical Neurology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45245