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Most MTDPS is caused by mutations in genes that disrupt deoxyribonucleotide metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed the whole\u2010exome sequencing of a hepato\u2010encephalopathy patient with MTDPS and functional analyses to determine the clinical significance of the identified variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, whole\u2010exome sequencing of a patient presenting with hepato\u2010encephalopathy and MTDPS identified a novel homozygous frameshift variant, c.13_29del (p.Trp6Profs*71) in <jats:italic>MICOS13<\/jats:italic>. MICOS13 (also known as QIL1, MIC13, or C19orf70) is a component of the MICOS complex, which plays crucial roles in the maintenance of cristae junctions at the mitochondrial inner membrane. We found loss of MICOS13 protein and fewer cristae structures in the mitochondria of fibroblasts derived from the patient. Stable expression of a wild\u2010type <jats:italic>MICOS13<\/jats:italic> cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that the novel c.13_29del (p.Trp6Profs*71) <jats:italic>MICOS13<\/jats:italic> variant causes hepato\u2010encephalopathy with MTDPS. We propose that <jats:italic>MICOS13<\/jats:italic> is classified as the cause of MTDPS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1427","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T10:34:56Z","timestamp":1596537296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A novel homozygous variant in <i>MICOS13<\/i>\/<i>QIL1<\/i> causes hepato\u2010encephalopathy with mitochondrial DNA depletion syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-1680","authenticated-orcid":false,"given":"Yoshihito","family":"Kishita","sequence":"first","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases Intractable Disease Research Center Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1998-7349","authenticated-orcid":false,"given":"Masaru","family":"Shimura","sequence":"additional","affiliation":[{"name":"Department of Metabolism Chiba Children's Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-2224","authenticated-orcid":false,"given":"Masakazu","family":"Kohda","sequence":"additional","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases Intractable Disease Research Center Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masumi","family":"Akita","sequence":"additional","affiliation":[{"name":"Division of Morphological Science Biomedical Research Center Saitama Medical University Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-2881","authenticated-orcid":false,"given":"Atsuko","family":"Imai\u2010Okazaki","sequence":"additional","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases Intractable Disease Research Center Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-6919","authenticated-orcid":false,"given":"Yukiko","family":"Yatsuka","sequence":"additional","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases Intractable Disease Research Center Juntendo University Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-3113","authenticated-orcid":false,"given":"Akira","family":"Ohtake","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; 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