{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:33Z","timestamp":1753869693829,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"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":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transcobalamin II (<jats:italic>TCN<\/jats:italic>2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Presentation<\/jats:title><jats:p>We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9\u2009months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G&gt;A \u2013 P(Met1I), affecting the acceptor site of intron 4 of the <jats:italic>TCN<\/jats:italic>2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In infants presenting with unexplained non\u2010specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for <jats:italic>TCN<\/jats:italic>2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2282","type":"journal-article","created":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T04:57:40Z","timestamp":1696654660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\u201cProgressive myoclonic ataxia and developmental\/epileptic encephalopathy associated with a novel homozygous mutation in <scp><i>TCN<\/i>2<\/scp> gene\u201d"],"prefix":"10.1002","volume":"12","author":[{"given":"Mohammed Ahmed Mohammed","family":"Oshi","sequence":"first","affiliation":[{"name":"Neurology Division Gaafar Ibnauf Children's Emergency Hospital  Khartoum Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaber","family":"Alfaifi","sequence":"additional","affiliation":[{"name":"Department of Child Health, College of Medicine University of Bisha  Bisha Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youssef Ali M.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Child Health, College of Medicine King Khalid University  Abha Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Fahad","family":"Aljabri","sequence":"additional","affiliation":[{"name":"Alhada Armed Forces Hospital  Taif Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-3838","authenticated-orcid":false,"given":"Naglaa M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Hepatology, Kasr Alainy Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jwaher","family":"Althopaity","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid A.","family":"Althobaiti","sequence":"additional","affiliation":[{"name":"Alhada Armed Forces Hospital  Taif Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah M.","family":"Almalki","sequence":"additional","affiliation":[{"name":"Alhada Armed Forces Hospital  Taif Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salma A. S.","family":"Abosabie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Julius\u2010Maximilians\u2010Universit\u00e4t W\u00fcrzburg  Wurzburg Bavaria Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A.","family":"Abosabie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan Sakr","family":"Sherbiny","sequence":"additional","affiliation":[{"name":"Department of Child Health, College of Medicine University of Bisha  Bisha Saudi Arabia"},{"name":"Department of pediatrics, Faculty of Medicine Zagazig University  Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif K.","family":"Almanjoomi","sequence":"additional","affiliation":[{"name":"Alhada Armed Forces Hospital  Taif Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enas A. A.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Hepatology, Kasr Alainy Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2006.10.016"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/15648265080292S117"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00531"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2008.00031.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2016.0834"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-4079(19)31264-6"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1992.tb06410.x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2009.12.003"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12012"},{"issue":"4","key":"e_1_2_13_11_1","first-page":"329","article-title":"Vitamin B12 in health and disease: Part I\u2014Inherited disorders of function, absorption, and transport","volume":"3","author":"Kapadia C. R.","year":"1995","journal-title":"The Gastroenterologist"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2020-0096"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-014-0112-3"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-021-01007-6"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000857"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.057810"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-021-09849-5"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9074-x"},{"issue":"12","key":"e_1_2_13_19_1","first-page":"868","article-title":"Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults","volume":"5","author":"Teplitsky V.","year":"2003","journal-title":"Israel Medical Association Journal"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.62.2.197"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.45.1.74"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-013-9664-5"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000685"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T12:25:17Z","timestamp":1706531117000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/mgg3.2282"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2282","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2023,10,6]]},"assertion":[{"value":"2023-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2282"}}