{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:27:26Z","timestamp":1787023646014,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"DOI":"10.1186\/s12920-026-02407-5","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:45:12Z","timestamp":1780915512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A founder variant in TANGO2 p.(Leu148Trp) in ten Palestinian families: clinical characterization and haplotype analysis of TANGO2 deficiency disorder"],"prefix":"10.1186","volume":"19","author":[{"given":"Christina","family":"Canavati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motee","family":"Ashhab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Rabie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Hreimat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin","family":"Shatrit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fouad","family":"Zahdeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania","family":"Dajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Atawneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Ali","family":"Alsharha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadirah","family":"Damseh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam","family":"Abu-Libdeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Dweikat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Handal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moien","family":"Kanaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2407_CR1","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1093\/nar\/gki033","volume":"33","author":"A Hamosh","year":"2005","unstructured":"Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005;33:514\u20137. https:\/\/doi.org\/10.1093\/nar\/gki033. Database issue:D.","journal-title":"Nucleic Acids Res"},{"key":"2407_CR2","doi-asserted-by":"publisher","first-page":"100352","DOI":"10.1016\/j.gim.2022.11.020","volume":"25","author":"CY Miyake","year":"2023","unstructured":"Miyake CY, Lay EJ, Soler-Alfonso C, Glinton KE, Houck KM, Tosur M, et al. Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients. Genet Med. 2023;25:100352. https:\/\/doi.org\/10.1016\/j.gim.2022.11.020.","journal-title":"Genet Med"},{"key":"2407_CR3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.ajhg.2015.12.008","volume":"98","author":"SR Lalani","year":"2016","unstructured":"Lalani SR, Liu P, Rosenfeld JA, Watkin LB, Chiang T, Leduc MS, et al. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. Am J Hum Genet. 2016;98:347\u201357. https:\/\/doi.org\/10.1016\/j.ajhg.2015.12.008.","journal-title":"Am J Hum Genet"},{"key":"2407_CR4","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.1038\/s41598-022-07076-9","volume":"12","author":"P Heiman","year":"2022","unstructured":"Heiman P, Mohsen A-W, Karunanidhi A, St Croix C, Watkins S, Koppes E, et al. Mitochondrial dysfunction associated with TANGO2 deficiency. Sci Rep. 2022;12:3045. https:\/\/doi.org\/10.1038\/s41598-022-07076-9.","journal-title":"Sci Rep"},{"key":"2407_CR5","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1002\/jimd.12312","volume":"44","author":"MP Milev","year":"2021","unstructured":"Milev MP, Saint-Dic D, Zardoui K, Klopstock T, Law C, Distelmaier F, et al. The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria. J Inherit Metab Dis. 2021;44:426\u201337. https:\/\/doi.org\/10.1002\/jimd.12312.","journal-title":"J Inherit Metab Dis"},{"key":"2407_CR6","doi-asserted-by":"publisher","first-page":"dmm050662","DOI":"10.1242\/dmm.050662","volume":"17","author":"M Sacher","year":"2024","unstructured":"Sacher M, DeLoriea J, Mehranfar M, Casey C, Naaz A, Gamberi C. TANGO2 deficiency disease is predominantly caused by a lipid imbalance. Dis Model Mech. 2024;17:dmm050662. https:\/\/doi.org\/10.1242\/dmm.050662.","journal-title":"Dis Model Mech"},{"key":"2407_CR7","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1016\/j.hrthm.2022.05.009","volume":"19","author":"CY Miyake","year":"2022","unstructured":"Miyake CY, Lay EJ, Beach CM, Ceresnak SR, Delauz CM, Howard TS, et al. Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises. Heart Rhythm. 2022;19:1673\u201381. https:\/\/doi.org\/10.1016\/j.hrthm.2022.05.009.","journal-title":"Heart Rhythm"},{"key":"2407_CR8","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1002\/jimd.12149","volume":"42","author":"E Jennions","year":"2019","unstructured":"Jennions E, Hedberg-Oldfors C, Berglund A-K, Kollberg G, T\u00f6rnhage C-J, Eklund EA, et al. TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism. J Inherit Metab Dis. 2019;42:898\u2013908. https:\/\/doi.org\/10.1002\/jimd.12149.","journal-title":"J Inherit Metab Dis"},{"key":"2407_CR9","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41436-018-0137-y","volume":"21","author":"JN Dines","year":"2019","unstructured":"Dines JN, Golden-Grant K, LaCroix A, Muir AM, Cintr\u00f3n DL, McWalter K, et al. TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants. Genet Med Off J Am Coll Med Genet. 2019;21:601\u20137. https:\/\/doi.org\/10.1038\/s41436-018-0137-y.","journal-title":"Genet Med Off J Am Coll Med Genet"},{"key":"2407_CR10","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/jimd.12314","volume":"44","author":"C-M B\u00e9rat","year":"2021","unstructured":"B\u00e9rat C-M, Montealegre S, Wiedemann A, Nuzum MLC, Blondel A, Debruge H, et al. Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect. J Inherit Metab Dis. 2021;44:415\u201325. https:\/\/doi.org\/10.1002\/jimd.12314.","journal-title":"J Inherit Metab Dis"},{"key":"2407_CR11","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/jimd.12585","volume":"46","author":"SE Sandkuhler","year":"2023","unstructured":"Sandkuhler SE, Zhang L, Meisner JK, Ghaloul-Gonzalez L, Beach CM, Harris D, et al. B-complex vitamins for patients with TANGO2-deficiency disorder. J Inherit Metab Dis. 2023;46:161\u20132. https:\/\/doi.org\/10.1002\/jimd.12585.","journal-title":"J Inherit Metab Dis"},{"key":"2407_CR12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ejmg.2014.01.003","volume":"57","author":"MM Sirdah","year":"2014","unstructured":"Sirdah MM. Consanguinity profile in the Gaza Strip of Palestine: large-scale community-based study. Eur J Med Genet. 2014;57:90\u20134. https:\/\/doi.org\/10.1016\/j.ejmg.2014.01.003.","journal-title":"Eur J Med Genet"},{"key":"2407_CR13","doi-asserted-by":"publisher","first-page":"S55","DOI":"10.1016\/S0140-6736(19)30641-5","volume":"393","author":"HJ Zawahrah","year":"2019","unstructured":"Zawahrah HJ, Moore MG, Saeed O, Tayem M, Shahin H, van Aalst JA. Demographics of consanguinity in Palestinians with orofacial clefts: a non-randomised longitudinal study. Lancet. 2019;393:S55. https:\/\/doi.org\/10.1016\/S0140-6736(19)30641-5.","journal-title":"Lancet"},{"issue":"19970211","key":"2407_CR14","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/(sici)1096-8628","volume":"68","author":"J Zlotogora","year":"1997","unstructured":"Zlotogora J. Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am J Med Genet. 1997;68(19970211):472\u20135. https:\/\/doi.org\/10.1002\/(sici)1096-8628. )68:4%3C472::aid-ajmg20%3E3.0.co;2-o.","journal-title":"Am J Med Genet"},{"key":"2407_CR15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1017\/S0021932008002940","volume":"41","author":"S Assaf","year":"2009","unstructured":"Assaf S, Khawaja M. Consanguinity trends and correlates in the Palestinian Territories. J Biosoc Sci. 2009;41:107\u201324. https:\/\/doi.org\/10.1017\/S0021932008002940.","journal-title":"J Biosoc Sci"},{"key":"2407_CR16","doi-asserted-by":"publisher","unstructured":"Ghanim M, Mosleh,Rami H et al. Anas, Amer, Johnny, Alqub, Malik, Jarrar, Yazun,. Assessment of Perceptions and Predictors Towards Consanguinity: A Cross-Sectional Study from Palestine. J Multidiscip Healthc. 2023;16:3443\u201353. https:\/\/doi.org\/10.2147\/JMDH.S433506.","DOI":"10.2147\/JMDH.S433506"},{"key":"2407_CR17","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/jimd.12579","volume":"46","author":"P Asadi","year":"2023","unstructured":"Asadi P, Milev MP, Saint-Dic D, Gamberi C, Sacher M. Vitamin B5, a coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in Drosophila and human cells. J Inherit Metab Dis. 2023;46:358\u201368. https:\/\/doi.org\/10.1002\/jimd.12579.","journal-title":"J Inherit Metab Dis"},{"key":"2407_CR18","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1002\/humu.24309","volume":"43","author":"S Gudmundsson","year":"2022","unstructured":"Gudmundsson S, Singer-Berk M, Watts NA, Phu W, Goodrich JK, Solomonson M, et al. Variant interpretation using population databases: Lessons from gnomAD. Hum Mutat. 2022;43:1012\u201330. https:\/\/doi.org\/10.1002\/humu.24309.","journal-title":"Hum Mutat"},{"key":"2407_CR19","doi-asserted-by":"publisher","unstructured":"Adzhubei I, Jordan DM, Sunyaev SR. Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2. Curr Protoc Hum Genet Editor Board Jonathan Haines Al. 2013;0 7:Unit7.20. https:\/\/doi.org\/10.1002\/0471142905.hg0720s76.","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"2407_CR20","doi-asserted-by":"publisher","first-page":"eadg7492","DOI":"10.1126\/science.adg7492","volume":"381","author":"J Cheng","year":"2023","unstructured":"Cheng J, Novati G, Pan J, Bycroft C, \u017demgulyt\u0117 A, Applebaum T, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023;381:eadg7492. https:\/\/doi.org\/10.1126\/science.adg7492.","journal-title":"Science"},{"key":"2407_CR21","doi-asserted-by":"publisher","first-page":"8857940","DOI":"10.1155\/2023\/8857940","volume":"2023","author":"JJ Hopkins","year":"2023","unstructured":"Hopkins JJ, Wakeling MN, Johnson MB, Flanagan SE, Laver TW. REVEL Is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants. Hum Mutat. 2023;2023:8857940. https:\/\/doi.org\/10.1155\/2023\/8857940.","journal-title":"Hum Mutat"},{"key":"2407_CR22","doi-asserted-by":"publisher","unstructured":"Fromer M, Purcell SM. Using XHMM Software to Detect Copy Number Variation in Whole-Exome Sequencing Data. Curr Protoc Hum Genet. 2014;81:7.23.1-7.23.21. https:\/\/doi.org\/10.1002\/0471142905.hg0723s81.","DOI":"10.1002\/0471142905.hg0723s81"},{"key":"2407_CR23","unstructured":"Schr\u00f6dinger,LLC. The PyMOL Molecular Graphics System, Version 3.0. Schr\u00f6dinger, LLC. https:\/\/pymol.org\/support.html."},{"key":"2407_CR24","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1002\/pro.3942","volume":"30","author":"CHM Rodrigues","year":"2021","unstructured":"Rodrigues CHM, Pires DEV, Ascher DB. DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations. Protein Sci Publ Protein Soc. 2021;30:60\u20139. https:\/\/doi.org\/10.1002\/pro.3942.","journal-title":"Protein Sci Publ Protein Soc"},{"key":"2407_CR25","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/ajmg.a.62543","volume":"188","author":"J Schymick","year":"2022","unstructured":"Schymick J, Leahy P, Cowan T, Ruzhnikov MRZ, Gates R, Fernandez L, et al. Variable clinical severity in TANGO2 deficiency: Case series and literature review. Am J Med Genet A. 2022;188:473\u201387. https:\/\/doi.org\/10.1002\/ajmg.a.62543.","journal-title":"Am J Med Genet A"},{"key":"2407_CR26","doi-asserted-by":"crossref","unstructured":"Abu-Libdeh B, Teebi AS. Genetic Disorders Among the Palestinians. 2010.","DOI":"10.1007\/978-3-642-05080-0_17"},{"key":"2407_CR27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/1750-1172-7-52","volume":"7","author":"L Romdhane","year":"2012","unstructured":"Romdhane L, Kefi R, Azaiez H, Ben Halim N, Dellagi K, Abdelhak S. Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East. Orphanet J Rare Dis. 2012;7:52. https:\/\/doi.org\/10.1186\/1750-1172-7-52.","journal-title":"Orphanet J Rare Dis"},{"key":"2407_CR28","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1136\/jmg.34.9.765","volume":"34","author":"J Zlotogora","year":"1997","unstructured":"Zlotogora J. Autosomal recessive diseases among Palestinian Arabs. J Med Genet. 1997;34:765\u20136. https:\/\/doi.org\/10.1136\/jmg.34.9.765.","journal-title":"J Med Genet"},{"key":"2407_CR29","doi-asserted-by":"publisher","unstructured":"e Calbiac H, Montealegre S, Straube M, Renault S, Debruge H, Chentout L, et al. TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning. Autophagy Rep. 2024;3:2306766, 27694127.2024.2306766 https:\/\/doi.org\/10.1080\/27694127.2024.2306766.","DOI":"10.1080\/27694127.2024.2306766"},{"key":"2407_CR30","doi-asserted-by":"publisher","first-page":"5871","DOI":"10.19102\/icrm.2024.15054","volume":"15","author":"B Walters","year":"2024","unstructured":"Walters B, McConkey N, Imundo JR. TANGO2: A Rare but Important Mutation. J Innov Card Rhythm Manag. 2024;15:5871\u20135. https:\/\/doi.org\/10.19102\/icrm.2024.15054.","journal-title":"J Innov Card Rhythm Manag"},{"key":"2407_CR31","doi-asserted-by":"publisher","first-page":"e171005","DOI":"10.1172\/jci.insight.171005","volume":"9","author":"W Xu","year":"2024","unstructured":"Xu W, Cao Y, Stephens SB, Arredondo MJ, Chen Y, Perez W, et al. Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder. JCI Insight. 2024;9:e171005. https:\/\/doi.org\/10.1172\/jci.insight.171005.","journal-title":"JCI Insight"},{"key":"2407_CR32","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.3390\/ijms24032585","volume":"24","author":"D Mantle","year":"2023","unstructured":"Mantle D, Lopez-Lluch G, Hargreaves IP. Coenzyme Q10 Metabolism: A Review of Unresolved Issues. Int J Mol Sci. 2023;24:2585. https:\/\/doi.org\/10.3390\/ijms24032585.","journal-title":"Int J Mol Sci"},{"key":"2407_CR33","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/cells7070084","volume":"7","author":"M Parra","year":"2018","unstructured":"Parra M, Stahl S, Hellmann H. Vitamin B6 and Its Role in Cell Metabolism and Physiology. Cells. 2018;7:84. https:\/\/doi.org\/10.3390\/cells7070084.","journal-title":"Cells"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-026-02407-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-026-02407-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-026-02407-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:09:03Z","timestamp":1787022543000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12920-026-02407-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2407"],"URL":"https:\/\/doi.org\/10.1186\/s12920-026-02407-5","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"assertion":[{"value":"2 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Institutional Review Board (IRB) of Bethlehem University [IRB00010698]. All procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent to participate was obtained from all participants and the parents\/legal guardians of minors.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for publication of their personal or clinical details along with any identifying images has been obtained from all the participants and the parents\/legal guardians of minors.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"131"}}