Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3'-end processing.

"the active site and regions proximal to it which directly contact the substrate are found in the carboxy domain of elac2 (a long form rnase z rnase z l ) and were superimposed onto the corresponding regions in the only available co-crystal structure of rnase z with pre-trna substrate from bacillus subtilis (pdb 4gcw; pellegrini li de la sierra-gallay piton gilet & condon 2012 ) 3 3 1 we investigated 13 families with a cohort of 13 infants most presenting with early-onset syndromic cardiomyopathy with hcm being present in 10 subjects dilated cardiomyopathy (dcm) in two subjects and one subject being reported without any cardiac problems."

"C. A. Powell, P. Rebelo‐Guiomar, and M. Minczuk were supported by Medical Research Council, UK (MC_U105697135 and MC_UU_00015/4). P. Rebelo‐Guiomar is supported by Fundação para a Ciência e a Tecnologia (PD/BD/105750/2014). M. Saoura , M. Pujantell, K.‐G. Pinnock, and L. Levinger were supported by the grant R15GM101620 from the NIH. L. Levinger is a member of the graduate programs in Biochemistry and Molecular and Cellular Biology, The City University of New York. R. McFarland and R. W. Taylor are supported by the Wellcome Center for Mitochondrial Research (203105/Z/16/Z), the MRC Center for Neuromuscular Diseases (G0601943), Newcastle University Center for Ageing and Vitality (supported by the Biotechnology and Biological Sciences Research Council and Medical Research Council [G016354/1]), the UK NIHR Biomedical Research Center in Age and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation, the MRC/ESPRC Newcastle Molecular Pathology Node, the Lily Foundation, and the UK National Health Service Highly Specialised Service for Rare Mitochondrial Disorders. C. L. Alston was supported by a National Institute for Health Research (NIHR) doctoral fellowship (NIHR‐HCS‐D12‐03‐04). R. Horvath is a Wellcome Investigator (109915/Z/15/Z), who receives support from the Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). A.A. receives funding for a PhD studentship from the Kuwait Civil Service Commission under the approval of the Kuwait Ministry of Health. D. Ghezzi was supported by the Telethon Foundation (grant GGP15041); the Pierfranco and Luisa Mariani Foundation; the E‐Rare project GENOMIT. H. Prokisch was supported by the German Bundesministerium für Bildung und Forschung (BMBF) and Horizon2020 through the E‐Rare project GENOMIT (01GM1603 and 01GM1207), through the German Network for mitochondrial disorders (mitoNET, 01GM1113C) and the EU Horizon2020 Collaborative Research Project SOUND (633974). The “Cell lines and DNA Bank of Genetic Movement Disorders and Mitochondrial Diseases” of the Telethon Network of Genetic Biobanks (grant GTB12001J) and the EuroBioBank Network supplied biological specimens. E. Bertini, R. Carrozzo, M. D. Nottia, and D. Verrigni are supported by the Italian Ministry of Health Ricerca Corrente. S. Rahman receives grant funding from Great Ormond Street Hospital Childrenʼs Charity and the Lily Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

"C. A. Powell, P. Rebelo‐Guiomar, and M. Minczuk were supported by Medical Research Council, UK (MC_U105697135 and MC_UU_00015/4). P. Rebelo‐Guiomar is supported by Fundação para a Ciência e a Tecnologia (PD/BD/105750/2014). M. Saoura , M. Pujantell, K.‐G. Pinnock, and L. Levinger were supported by the grant R15GM101620 from the NIH. L. Levinger is a member of the graduate programs in Biochemistry and Molecular and Cellular Biology, The City University of New York. R. McFarland and R. W. Taylor are supported by the Wellcome Center for Mitochondrial Research (203105/Z/16/Z), the MRC Center for Neuromuscular Diseases (G0601943), Newcastle University Center for Ageing and Vitality (supported by the Biotechnology and Biological Sciences Research Council and Medical Research Council [G016354/1]), the UK NIHR Biomedical Research Center in Age and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation, the MRC/ESPRC Newcastle Molecular Pathology Node, the Lily Foundation, and the UK National Health Service Highly Specialised Service for Rare Mitochondrial Disorders. C. L. Alston was supported by a National Institute for Health Research (NIHR) doctoral fellowship (NIHR‐HCS‐D12‐03‐04). R. Horvath is a Wellcome Investigator (109915/Z/15/Z), who receives support from the Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). A.A. receives funding for a PhD studentship from the Kuwait Civil Service Commission under the approval of the Kuwait Ministry of Health. D. Ghezzi was supported by the Telethon Foundation (grant GGP15041); the Pierfranco and Luisa Mariani Foundation; the E‐Rare project GENOMIT. H. Prokisch was supported by the German Bundesministerium für Bildung und Forschung (BMBF) and Horizon2020 through the E‐Rare project GENOMIT (01GM1603 and 01GM1207), through the German Network for mitochondrial disorders (mitoNET, 01GM1113C) and the EU Horizon2020 Collaborative Research Project SOUND (633974). The “Cell lines and DNA Bank of Genetic Movement Disorders and Mitochondrial Diseases” of the Telethon Network of Genetic Biobanks (grant GTB12001J) and the EuroBioBank Network supplied biological specimens. E. Bertini, R. Carrozzo, M. D. Nottia, and D. Verrigni are supported by the Italian Ministry of Health Ricerca Corrente. S. Rahman receives grant funding from Great Ormond Street Hospital Childrenʼs Charity and the Lily Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The study was conceptualized by M. M., L. L, H. P., R. W. T; formal analysis was performed by M. S., C. A. P., R. K., B. L., M. M., L. L., H. P., R. W. T., and D. G.; Funding acquisition was provided by M. M., L. L, H. P., R. W. T, D. G., E. B., and R. H.; Investigation was performed by M. S., C. A. P., P. R‐.G., R. K., D. G., F. I., E. L., M. P., K‐G. P., A. A., H. H. A‐B, B. A. C. A. L, D. B., M. D. N, D. V., and S. R.; Methodology was given by M. S., L. L., M. M., C. A. P.; Project administration was managed by M. M., L. L, H. P., R. W. T, D. G., E. B., and E. H.; Resources were provided by M. A. D, S. S., P. B., M. A., R. C., A. G., E. H., D. G., S. R., R. H. R. M.; Supervision was done by M. M., L. L, H. P. R. W. T, D. G., E. B., and E. H. Validation was done by M. M., L. L, H. P. R. W. T.; Visualization was provided by P.R‐G., M.S., C.A.P, L.L., M.M.; the orginal draft was written by M. M., L. L., R. W. T., and R. M.; all authors wrote, reviewed and edited the article."