@misc{10481/63188,
year = {2015},
month = {6},
url = {http://hdl.handle.net/10481/63188},
abstract = {Myoclonus-dystonia (M-D) is a rare movement disorder characterized by a combination of non-epileptic myoclonic jerks and dystonia. SGCE mutations represent a major cause for familial M-D being responsible for 30%–50% of cases. After excluding SGCE mutations, we identified through a combination of linkage analysis and whole-exome sequencing KCTD17 c.434 G>A p.(Arg145His) as the only segregating variant in a dominant British pedigree with seven subjects affected by M-D. A subsequent screening in a cohort of M-D cases without mutations in SGCE revealed the same KCTD17 variant in a German family. The clinical presentation of the KCTD17-mutated cases was distinct from the phenotype usually observed in M-D due to SGCE mutations. All cases initially presented with mild myoclonus affecting the upper limbs. Dystonia showed a progressive course, with increasing severity of symptoms and spreading from the cranio-cervical region to other sites. KCTD17 is abundantly expressed in all brain regions with the highest expression in the putamen. Weighted gene co-expression network analysis, based on mRNA expression profile of brain samples from neuropathologically healthy individuals, showed that KCTD17 is part of a putamen gene network, which is significantly enriched for dystonia genes. Functional annotation of the network showed an over-representation of genes involved in post-synaptic dopaminergic transmission. Functional studies in mutation bearing fibroblasts demonstrated abnormalities in endoplasmic reticulum-dependent calcium signaling. In conclusion, we demonstrate that the KCTD17 c.434 G>A p.(Arg145His) mutation causes autosomal dominant M-D. Further functional studies are warranted to further characterize the nature of KCTD17 contribution to the molecular pathogenesis of M-D.},
organization = {Medical Research Council UK (MRC)

Wellcome Trust
	
WT089698/Z/09/Z},
organization = {Bachman-Strauss Dystonia Parkinsonism Foundation},
organization = {Department of Health's NIHR Biomedical Research Center},
organization = {Dystonia Medical Research Foundation (DMRF)},
organization = {Herman and Lilly Schilling Foundation},
organization = {Reta Lila Weston Trust},
organization = {Spanish Government},
organization = {Cei-BioTic},
organization = {University of Granada},
organization = {Academy of Medical Sciences (AMS)
	
AMS-SGCL11-Peall},
organization = {Medical Research Council UK (MRC)
	
MR/L501554/1
G1100643
MC_G1000735
MC_PC_09003
G0700943
MC_G0901330},
organization = {National Institute for Health Research (NIHR)
	
2042
NF-SI-0513-10064
NF-SI-0507-10376},
organization = {Parkinson's UK
	
H-1006},
publisher = {Elsevier},
title = {A Missense Mutation in KCTD17 Causes Autosomal Dominant Myoclonus-Dystonia},
doi = {10.1016/j.ajhg.2015.04.008},
author = {Mencacci, Niccolo E. and Bandrés Ciga, Sara},
}