{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:18Z","timestamp":1772160078321,"version":"3.50.1"},"reference-count":11,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1240\/16\u20101"],"award-info":[{"award-number":["KU 1240\/16\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,9]]},"abstract":"Abstract<\/jats:title>\n \n Biallelic variants in\n PISD<\/jats:italic>\n cause a phenotypic spectrum ranging from short stature with spondyloepimetaphyseal dysplasia (SEMD) to a multisystem disorder affecting eyes, ears, bones, and brain.\n PISD<\/jats:italic>\n encodes the mitochondrial\u2010localized enzyme phosphatidylserine decarboxylase. The PISD precursor is self\u2010cleaved to generate a heteromeric mature enzyme that converts phosphatidylserine to the phospholipid phosphatidylethanolamine. We describe a 17\u2010year\u2010old male patient, born to unrelated healthy parents, with disproportionate short stature and SEMD, featuring platyspondyly, prominent epiphyses, and metaphyseal dysplasia. Trio genome sequencing revealed compound heterozygous\n PISD<\/jats:italic>\n variants c.569C>T; p.(Ser190Leu) and c.799C>T; p.(His267Tyr) in the patient. Investigation of fibroblasts showed similar levels of the PISD precursor protein in both patient and control cells. However, patient cells had a significantly higher proportion of fragmented mitochondria compared to control cells cultured under basal condition and after treatment with 2\u2010deoxyglucose that represses glycolysis and stimulates respiration. Structural data from the PISD orthologue in\n Escherichia coli<\/jats:italic>\n suggest that the amino acid substitutions Ser190Leu and His267Tyr likely impair PISD's autoprocessing activity and\/or phosphatidylethanolamine biosynthesis. Based on the data, we propose that the novel\n PISD<\/jats:italic>\n p.(Ser190Leu) and p.(His267Tyr) variants likely act as hypomorphs and underlie the pure skeletal phenotype in the patient.\n <\/jats:p>","DOI":"10.1111\/cge.14549","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:55:14Z","timestamp":1716789314000},"page":"360-366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel biallelic\n PISD<\/i>\n missense variants cause spondyloepimetaphyseal dysplasia with disproportionate short stature and fragmented mitochondrial morphology"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6489-1680","authenticated-orcid":false,"given":"Line","family":"Aagaard Nolting","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Center for Rare Diseases Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tess","family":"Holling","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Center for Intractable Diseases Saitama Medical University Hospital Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Ek","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads","family":"Bak","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merete","family":"Ljungberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Rare Diseases Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-1278","authenticated-orcid":false,"given":"Hanne","family":"Hove","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Rare Diseases Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2017.04.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.642413"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00049\u201017"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506510200"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.434183"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100595\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23693"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900353"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2020.04.006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.058516"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21\u201011\u20100558\u2010T"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T22:13:15Z","timestamp":1723500795000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/cge.14549"],"URL":"https:\/\/doi.org\/10.1111\/cge.14549","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14549\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14549\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14549\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14549\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14549\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14549\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,27]]},"assertion":[{"value":"2024-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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