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

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...

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Vydáno v:	eLife Ročník 9
Hlavní autoři:	Lekszas, Caroline, Foresti, Ombretta, Raote, Ishier, Liedtke, Daniel, König, Eva-Maria, Nanda, Indrajit, Vona, Barbara, De Coster, Peter, Cauwels, Rita, Malhotra, Vivek, Haaf, Thomas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England eLife Science Publications, Ltd 26.02.2020 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Témata:	Alleles Ankylosing spondylitis Aryl Hydrocarbon Receptor Nuclear Translocator - genetics Binding sites Cell Biology Cell Line, Tumor collage secretion Collagen Collagen (type I) Collagen - metabolism Dentinogenesis Dentinogenesis imperfecta Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Disabilities Diseases Displays (Marketing) Endoplasmic reticulum Endoplasmic Reticulum - metabolism Enhancer Elements, Genetic Exons Families & family life Family Genetic aspects Golgi apparatus Golgi Apparatus - metabolism Hearing loss Human Biology and Medicine Humans Insulin Intellectual disabilities Messenger RNA mRNA Musculoskeletal abnormalities Mutation Parents & parenting Protein Transport Proteins Pruritus RNA Scoliosis Secretion Short Report Short stature TANGO1 Whole Exome Sequencing California dentinogenesis imperfecta human biology cell biology TANGO1 diabetes mellitus medicine human collage secretion
ISSN:	2050-084X, 2050-084X
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work. These authors also contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.51319