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The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort.

Mencacci, NE; R'bibo, L; Bandres-Ciga, S; Carecchio, M; Zorzi, G; Nardocci, N; Garavaglia, B; Batla, A; Bhatia, KP; Pittman, AM; et al. Mencacci, NE; R'bibo, L; Bandres-Ciga, S; Carecchio, M; Zorzi, G; Nardocci, N; Garavaglia, B; Batla, A; Bhatia, KP; Pittman, AM; Hardy, J; Weissbach, A; Klein, C; Gasser, T; Lohmann, E; Wood, NW (2015) The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort. Hum Mol Genet, 24 (18). pp. 5326-5329. ISSN 1460-2083 https://doi.org/10.1093/hmg/ddv255
SGUL Authors: Pittman, Alan Michael

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Abstract

Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ∼30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregation Consortium). The variant was detected in a single sporadic case with M-D, but in none of the 146 probands with familial M-D. Overall, the variant was present at comparable frequencies in M-D cases (1 out of 520; 0.19%) and healthy controls (1 out of 489; 0.2%). A similar frequency of the variant was also reported in all publicly available databases. These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D.

Item Type: Article
Additional Information: © The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Alleles, Amino Acid Substitution, Calcium Channels, N-Type, Codon, Cohort Studies, Dystonic Disorders, Europe, Exome, Female, Gene Frequency, Genetic Association Studies, Genotype, High-Throughput Nucleotide Sequencing, Humans, Male, Mutation, Humans, Dystonic Disorders, Calcium Channels, N-Type, Codon, Cohort Studies, Amino Acid Substitution, Gene Frequency, Genotype, Mutation, Alleles, Europe, Female, Male, Genetic Association Studies, High-Throughput Nucleotide Sequencing, Exome, 06 Biological Sciences, 11 Medical And Health Sciences, Genetics & Heredity
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Hum Mol Genet
ISSN: 1460-2083
Language: eng
Dates:
DateEvent
15 September 2015Published
8 July 2015Published Online
1 July 2015Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
RC2 HL102923NHLBI NIH HHSUNSPECIFIED
UC2 HL102926NHLBI NIH HHSUNSPECIFIED
UC2 HL103010NHLBI NIH HHSUNSPECIFIED
RC2 HL102926NHLBI NIH HHSUNSPECIFIED
WT089698/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_G1000735Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
089698Wellcome Trusthttp://dx.doi.org/10.13039/100004440
RC2 HL102924NHLBI NIH HHSUNSPECIFIED
UC2 HL102923NHLBI NIH HHSUNSPECIFIED
UC2 HL102924NHLBI NIH HHSUNSPECIFIED
RC2 HL103010NHLBI NIH HHSUNSPECIFIED
RC2 HL102925NHLBI NIH HHSUNSPECIFIED
UC2 HL102925NHLBI NIH HHSUNSPECIFIED
PubMed ID: 26157024
Web of Science ID: WOS:000361317200021
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111066
Publisher's version: https://doi.org/10.1093/hmg/ddv255

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