{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:54Z","timestamp":1792788774720,"version":"4.5.0"},"reference-count":42,"publisher":"Life Science Alliance, LLC","issue":"2","license":[{"start":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:00:00Z","timestamp":1552262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003206","name":"Alberta Children\u2019s Hospital Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003206","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01GM111548"],"award-info":[{"award-number":["R01GM111548"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation Graduate Research Fellowship","award":["DGE1746891"],"award-info":[{"award-number":["DGE1746891"]}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>\n                    Exome sequencing of two sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the\n                    <jats:italic>PISD<\/jats:italic>\n                    gene, encoding the phosphatidylserine decarboxylase enzyme that converts phosphatidylserine to phosphatidylethanolamine (PE) in the inner mitochondrial membrane (IMM). Decreased conversion of phosphatidylserine to PE in patient fibroblasts is consistent with impaired phosphatidylserine decarboxylase (PISD) enzyme activity. Meanwhile, as evidence for mitochondrial dysfunction, patient fibroblasts exhibited more fragmented mitochondrial networks, enlarged lysosomes, decreased maximal oxygen consumption rates, and increased sensitivity to 2-deoxyglucose. Moreover, treatment with lyso-PE, which can replenish the mitochondrial pool of PE, and genetic complementation restored mitochondrial and lysosome morphology in patient fibroblasts. Functional characterization of the\n                    <jats:italic>PISD<\/jats:italic>\n                    variants demonstrates that the maternal variant causes an alternative splice product. Meanwhile, the paternal variant impairs autocatalytic self-processing of the PISD protein required for its activity. Finally, evidence for impaired activity of mitochondrial IMM proteases suggests an explanation as to why the phenotypes of these\n                    <jats:italic>PISD<\/jats:italic>\n                    patients resemble recently described \u201cmitochondrial chaperonopathies.\u201d Collectively, these findings demonstrate that\n                    <jats:italic>PISD<\/jats:italic>\n                    is a novel mitochondrial disease gene.\n                  <\/jats:p>","DOI":"10.26508\/lsa.201900353","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T16:45:22Z","timestamp":1552322722000},"page":"e201900353","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["<i>PISD<\/i>\n                    is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes"],"prefix":"10.26508","volume":"2","author":[{"given":"Tian","family":"Zhao","sequence":"first","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin M","family":"Goedhart","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingdewinde N","family":"Sam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 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Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan E","family":"Lamont","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois P","family":"Bernier","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sinasac","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine, University 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