Journal article
Authors list: Milev, Miroslav P.; Stanga, Daniela; Schaenzer, Anne; Nascimento, Andres; Saint-Dic, Djenann; Ortez, Carlos; Natera-de Benito, Daniel; Gonzalez Barrios, Desire; Colomer, Jaume; Badosa, Carmen; Jou, Cristina; Gallano, Pia; Gonzalez-Quereda, Lidia; Topf, Ana; Johnson, Katherine; Straub, Volker; Hahn, Andreas; Sacher, Michael; Jimenez-Mallebrera, Cecilia
Publication year: 2019
Journal: Scientific Reports
Volume number: 9
ISSN: 2045-2322
Open access status: Gold
DOI Link: https://doi.org/10.1038/s41598-019-50415-6
Publisher: Nature Research
Abstract:
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.
Citation Styles
Harvard Citation style: Milev, M., Stanga, D., Schaenzer, A., Nascimento, A., Saint-Dic, D., Ortez, C., et al. (2019) Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein, Scientific Reports, 9, Article 14036. https://doi.org/10.1038/s41598-019-50415-6
APA Citation style: Milev, M., Stanga, D., Schaenzer, A., Nascimento, A., Saint-Dic, D., Ortez, C., Natera-de Benito, D., Gonzalez Barrios, D., Colomer, J., Badosa, C., Jou, C., Gallano, P., Gonzalez-Quereda, L., Topf, A., Johnson, K., Straub, V., Hahn, A., Sacher, M., & Jimenez-Mallebrera, C. (2019). Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein. Scientific Reports. 9, Article 14036. https://doi.org/10.1038/s41598-019-50415-6
