Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion

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• dc.contributor.author Lekszas, Caroline
• dc.contributor.author Foresti, Ombretta
• dc.contributor.author Raote, Ishier
• dc.contributor.author Liedtke, Daniel
• dc.contributor.author König, Eva Maria
• dc.contributor.author Nanda, Indrajit
• dc.contributor.author Vona, Barbara
• dc.contributor.author Coster, Peter de
• dc.contributor.author Cauwels, Rita
• dc.contributor.author Malhotra, Vivek
• dc.contributor.author Haaf, Thomas
• dc.date.accessioned 2020-11-18T07:04:56Z
• dc.date.available 2020-11-18T07:04:56Z
• dc.date.issued 2020
• dc.description.abstract The transport and Golgi organization 1 (TANGO1) proteins play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at endoplasmic reticulum (ER) exit sites, where it binds bulky cargo within the ER lumen and recruits membranes from the ER Golgi intermediate compartment to create an exit route for their export. Here we report the first TANGO1-associated syndrome in humans. A synonymous substitution that results in exon eight skipping in most mRNA molecules, ultimately leading to a truncated TANGO1 protein was identified as disease-causing mutation. The four homozygously affected sons of a consanguineous family display severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the corresponding truncated TANGO1 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1 impairs cellular collagen I secretion.
• dc.format.mimetype application/pdf
• dc.identifier.citation Lekszas C, Foresti O, Raote I, Liedtke D, König EM, Nanda I, Vona B, De Coster P, Cauwels R, Malhotra V, Haaf T. Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion. Elife. 2020; 9:e51319. DOI: 10.7554/eLife.51319
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.51319
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/45796
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.ispartof Elife. 2020; 9:e51319
• dc.rights © 2020, Lekszas et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword TANGO1
• dc.subject.keyword Cell biology
• dc.subject.keyword Collage secretion
• dc.subject.keyword Dentinogenesis imperfecta
• dc.subject.keyword Diabetes mellitus
• dc.subject.keyword Human
• dc.subject.keyword Human biology
• dc.subject.keyword Medicine
• dc.title Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion