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Lookup NU author(s): Dr Ana TopfORCiD,
Dr Katherine JohnsonORCiD,
Professor Volker StraubORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
TRAPPC11 was identified as a component of the TRAPP III complex that functions in membrane trafficking and autophagy. Variants in TRAPPC11 have been reported to be associated with a broad spectrum of phenotypes but all affected individuals display muscular pathology. Identifying additional variants will further our understanding of the clinical spectrum of phenotypes and will reveal regions of the protein critical for its functions. Here we report three individuals from unrelated families that have bi-allellic TRAPPC11 variants. Subject 1 harbors a compound heterozygous variant (c.1287 + 5G > A and c.3379_3380insT). The former variant results in a partial deletion of the foie gras domain (p.Ala372_Ser429del), while the latter variant results in a frame-shift and extension at the carboxy terminus (p.Asp1127Valfs*47). Subjects 2 and 3 both harbour a homozygous missense variant (c.2938G > A; p.Gly980Arg). Fibroblasts from all three subjects displayed membrane trafficking defects manifested as delayed endoplasmic reticulum (ER)-to-Golgi transport and/or a delay in protein exit from the Golgi. All three individuals also show a defect in glycosylation of an ER-resident glycoprotein. However, only the compound heterozygous subject displayed an autophagic flux defect. Collectively, our characterization of these individuals with bi-allelic TRAPPC11 variants highlights the functional importance of the carboxy-terminal portion of the protein.
Author(s): Milev MP, Stanga D, Schanzer A, Nascimento A, Saint-Dic D, Ortez C, Benito DN, Barrios DG, Colomer J, Badosa C, Jou C, Gallano P, Gonzalez-Quereda L, Topf A, Johnson K, Straub V, Hahn A, Sacher M, Jimenez-Mallebrera C
Publication type: Article
Publication status: Published
Journal: Scientific reports
Online publication date: 01/10/2019
Acceptance date: 11/09/2019
Date deposited: 14/10/2019
ISSN (electronic): 2045-2322
PubMed id: 31575891
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