Supplemental Data
Document S1. Figures S1–S8 and Table S1
Document S2. Article plus Supplemental Data

Web Resources
The URLs for data presented herein are as follows:dbSNP, http://www.ncbi.nlm.nih.gov/projects/SNP/
Human Genome Variation Society, http://www.hgvs.org/mutnomen/
Online Mendelian Inheritance in Man (OMIM), http://www.omim.org/
NHLBI Exome Sequencing Project (ESP) Exome Variant Server, http://evs.gs.washington.edu/EVS/
RefSeq, http://www.ncbi.nlm.nih.gov/RefSeq

Acknowledgments
We thank Carola G.M. van Berkel and Gigliola Fagiolari for their excellent technical support. We acknowledge the “Cell lines and DNA Bank of Paediatric Movement Disorders and Neurodegenerative Diseases” and the “Bank of muscle tissue, peripheral nerve, DNA and cell culture” of the Telethon Network of Genetic Biobanks (grant GTB12001J) and the EurobiobanK Network. This work was supported by Fondazione Telethon grants GGP11011 and GPP10005; the Italian Ministry of Health (GR2010–2316392); CARIPLO grant 2011/0526; the Pierfranco and Luisa Mariani Foundation of Italy; the Italian Association of Mitochondrial Disease Patients and Families (Mitocon); the European Research Council (ERC) Advanced Grant FP7-322424; the Impulse and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Health in an Ageing Society (HA-215) and the German Federal Ministry of Education and Research (BMBF)-funded German Center for Diabetes Research (DZD e.V.) and Systems Biology of Metabotypes grant (SysMBo #0315494A), the grant RF-INN-2007-634163 of the Italian Ministry of Health, the BMBF-funded German Network for Mitochondrial Disorders (mitoNET #01GM1113C), and the E-Rare project GENOMIT (01GM1207 and FWF I 920-B13) Medical Research Council, UK. T.E.M.A. and M.S.v.d.K. were supported by the Dutch Organisation for Scientific Research (ZonMw, TOP grant 91211005). R.W.T. is funded by a Wellcome Trust Strategic Award (096919/Z/11/Z), the MRC Centre for Neuromuscular Diseases (G0601943), the Lily Foundation, and the UK NHS Highly Specialised “Rare Mitochondrial Disorders of Adults and Children” Service. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).