{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:43:09Z","timestamp":1765546989416,"version":"3.40.5"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1155244"],"award-info":[{"award-number":["GNT1155244"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The C\u2010terminal binding protein 1 (CTBP1) functions as a transcriptional corepressor in vertebrates and has been identified to have critical roles in nervous system growth and development. Pathogenic variants in the <jats:italic>CTBP1<\/jats:italic> gene has been shown to cause hypotonia, ataxia, developmental delay and tooth enamel defect syndrome (HADDTS). There have only been 16 cases reported to date with heterozygous, pathogenic variants in <jats:italic>CTBP1<\/jats:italic> manifesting with a neurodevelopmental phenotype. We report a further case of a pathogenic, heterozygous, de novo variant in <jats:italic>CTBP1<\/jats:italic> identified by whole exome sequencing in a female with the typical phenotype of global developmental delay, hypotonia, cerebellar dysfunction and failure to thrive. Additionally, muscle biopsy demonstrates evidence of a respiratory chain defect, only previously reported once in the literature. This supports the role of CTBP1 in maintenance of normal mitochondrial activity and highlights the importance of considering secondary mitochondrial dysfunction in genes not directly involved in the mitochondrial respiratory chain.<\/jats:p>","DOI":"10.1002\/jmd2.12326","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T06:09:51Z","timestamp":1661407791000},"page":"546-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial respiratory chain dysfunction in a patient with a heterozygous de novo <scp><i>CTBP1<\/i><\/scp> variant"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-6306","authenticated-orcid":false,"given":"Wui\u2010Kwan","family":"Wong","sequence":"first","affiliation":[{"name":"TY Nelson Department of Neurology and Neurosurgery The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-1654","authenticated-orcid":false,"given":"Shanti","family":"Balasubramaniam","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Discipline of Genomic Medicine, Sydney Medical School University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel S. H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Histopathology The Children's Hospital at Westmead  Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Thorburn","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"},{"name":"Victorian Clinical Genetics Services  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"McFarland","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"},{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders Newcastle upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Troedson","sequence":"additional","affiliation":[{"name":"TY Nelson Department of Neurology and Neurosurgery The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-019-00578-1"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.562292"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-016-0482-4"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.06.335"},{"issue":"1","key":"e_1_2_13_6_1","first-page":"S77","article-title":"An unusual clinical presentation of CTBP1\u2010related syndrome associating muscle dystrophy, cerebellar ataxia and paralytic ileus","volume":"30","author":"El Houwayek E","year":"2020","journal-title":"Neuromusc Disorders"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-021-01315-0"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000187"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000321"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e3181ef42c1"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000446586"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000517870"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/609213"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2006.04.001"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510x(93)90108\u2010b"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.186"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000033795.17156.00"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12326","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12326","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T03:05:57Z","timestamp":1692673557000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/jmd2.12326"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12326","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"type":"print","value":"2192-8312"},{"type":"electronic","value":"2192-8312"}],"subject":[],"published":{"date-parts":[[2022,8,24]]},"assertion":[{"value":"2022-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}