{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T16:53:34Z","timestamp":1777222414640,"version":"3.51.4"},"reference-count":10,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,7]]},"abstract":"Abstract<\/jats:title>Ornithine transcarbamylase deficiency (OTCD) is an X\u2010linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%\u201390% of the causative variants are identified by Sanger sequencing or multiplex ligation\u2010dependent probe amplification (MLPA) of the OTC<\/jats:italic> gene. A 23\u2010year\u2010old male with biochemical evidence of OTCD was referred for molecular analysis. Initial Sanger sequencing yielded no pathogenic variants. MLPA testing raised suspicion of a mosaic deletion of exon 1; however, high\u2010resolution microarray did not identify a copy number variant on the X chromosome. Sequencing over the suspected breakpoint detected a hemizygous likely pathogenic promoter variant, c.\u2010106C\u2009>\u2009A, which was located within the MLPA probe binding site. Subsequently, historical patients referred to our centre, without a molecular aetiology for their OTCD, were re\u2010sequenced with these primers and this variant was also identified in two additional unrelated males. All three patients described in this case series have the late\u2010onset disease. Two presented at 5\u2009years of age with vomiting, whilst the other was managed from birth based on a family history of late\u2010onset OTCD. One patient required liver transplantation due to recurrent decompensations; the other two are managed with a protein\u2010restricted diet. All three patients have not sustained any significant neurological insults and are functioning well as adults. These cases support screening of the promoter region within the OTC<\/jats:italic> gene, particularly if a molecular basis has not been elucidated by MLPA or sequencing of the coding regions.<\/jats:p>","DOI":"10.1002\/jmd2.12289","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T10:19:53Z","timestamp":1649758793000},"page":"271-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A serendipitous journey to a promoter variant: The c.\u2010106C<\/scp>>A variant and its role in late\u2010onset ornithine transcarbamylase deficiency"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7926-8576","authenticated-orcid":false,"given":"Ashley","family":"Hertzog","sequence":"first","affiliation":[{"name":"NSW Biochemical Genetics Service The Children's Hospital at Westmead Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthavan","family":"Selvanathan","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Halligan","sequence":"additional","affiliation":[{"name":"Metabolic Unit Women's and Children's Hospital Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Fazio","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit Royal Melbourne Hospital Parkville Victoria Australia"},{"name":"Melbourne Medical School University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"de Jong","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit Royal Melbourne Hospital Parkville Victoria Australia"},{"name":"Melbourne Medical School University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drago","family":"Bratkovic","sequence":"additional","affiliation":[{"name":"Metabolic Unit Women's and Children's Hospital Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaustuv","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead Westmead New South Wales Australia"},{"name":"Disciplines of Genomic Medicine and Child and Adolescent Health Faculty of Medicine and Health, University of Sydney Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adviye Ayper","family":"Tolun","sequence":"additional","affiliation":[{"name":"NSW Biochemical Genetics Service The Children's Hospital at Westmead Westmead New South Wales Australia"},{"name":"Disciplines of Genomic Medicine and Child and Adolescent Health Faculty of Medicine and Health, University of Sydney Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Bennetts","sequence":"additional","affiliation":[{"name":"Disciplines of Genomic Medicine and Child and Adolescent Health Faculty of Medicine and Health, University of Sydney Sydney New South Wales Australia"},{"name":"Department of Molecular Genetics Western Sydney Genetics Program, The Children's Hospital at Westmead Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Fisk","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Western Sydney Genetics Program, The Children's Hospital at Westmead Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Lichter\u2010KoneckiU CaldovicL MorizonoHet al. Ornithine Transcarbamylase Deficiency. In GeneReviews\u00ae Adam MP Ardinger HH Pagon RA et al. eds. University of Washington 1993."},{"key":"e_1_2_11_3_1","first-page":"1","article-title":"Late\u2010onset ornithine transcarbamylase deficiency: an under recognized cause of metabolic encephalopathy","volume":"2","author":"Rush ET","year":"2014","journal-title":"SAGE Open Med Case Rep"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0266-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.54"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2015.04.003"},{"key":"e_1_2_11_7_1","first-page":"437","article-title":"Applying multiplex ligation\u2010dependent probe amplification in the diagnosis of 5 cases with ornithine transcarbamylase deficiency","volume":"54","author":"Gong ZW","year":"2016","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"e_1_2_11_8_1","first-page":"229","article-title":"Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation","volume":"53","author":"Ogino W","year":"2007","journal-title":"Kobe J Med Sci"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100706"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23394"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439-018-0022-x"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12289","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12289","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:50:34Z","timestamp":1692679834000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,12]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/jmd2.12289"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12289","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,12]]},"assertion":[{"value":"2022-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}