The online version of this article (doi:10.1186/1750-1326-9-44) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
KO carried out the molecular genetic studies and drafted the manuscript. MGH, SR, AIS-O, CL, RLW, OLB, XW and YA carried out the molecular genetic studies and data analysis. MGH performed all statistical analysis. SF, NG-R, RU, RR, WPC, ZKW and DWD made substantial contributions to acquisition of patient material and data. OAR conceived of the study, obtained study funding, participated in its design and coordination and drafted the manuscript. All authors participated in the interpretation of results, read and approved the final manuscript.
Loss of function COQ2 mutations results in primary CoQ10 deficiency. Recently, recessive mutations of the COQ2 gene have been identified in two unrelated Japanese families with multiple system atrophy (MSA). It has also been proposed that specific heterozygous variants in the COQ2 gene may confer susceptibility to sporadic MSA. To assess the frequency of COQ2 variants in patients with MSA, we sequenced the entire coding region and investigated all exonic copy number variants of the COQ2 gene in 97 pathologically-confirmed and 58 clinically-diagnosed MSA patients from the United States.
We did not find any homozygous or compound heterozygous pathogenic COQ2 mutations including deletion or multiplication within our series of MSA patients. In two patients, we identified two heterozygous COQ2 variants (p.S54W and c.403 + 10G > T) of unknown significance, which were not observed in 360 control subjects. We also identified one heterozygous carrier of a known loss of function p.S146N substitution in a severe MSA-C pathologically-confirmed patient.
The COQ2 p.S146N substitution has been previously reported as a pathogenic mutation in primary CoQ10 deficiency (including infantile multisystem disorder) in a recessive manner. This variant is the third primary CoQ10 deficiency mutation observed in an MSA case (p.R387X and p.R197H). Therefore it is possible that in the heterozygous state it may increase susceptibility to MSA. Further studies, including reassessing family history in patients of primary CoQ10 deficiency for the possible occurrence of MSA, are now warranted to resolve the role of COQ2 variation in MSA.
Additional file 1: For variants of COQ2 observed in this study, comparisons of MSA patients with controls, with EVS data, and with 1000 Genomes data.(DOCX 21 KB)13024_2014_554_MOESM1_ESM.docx
Authors’ original file for figure 113024_2014_554_MOESM2_ESM.tif
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- Analysis of COQ2gene in multiple system atrophy
Michael G Heckman
Alexandra I Soto-Ortolaza
Ronald L Walton
William P Cheshire
Zbigniew K Wszolek
Dennis W Dickson
Owen A Ross
- BioMed Central
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