Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation

  • Hum Mutat. 2017 Feb;38(2):148-151. doi: 10.1002/humu.23145.
Leslie Matalonga  1 ,  Miren Bravo  1 ,  Carla Serra-Peinado  2 ,  Elisabeth García-Pelegrí  1 ,  Olatz Ugarteburu  1 ,  Silvia Vidal  1 ,  Maria Llambrich  1 ,  Ester Quintana  1 ,  Pedro Fuster-Jorge  3 ,  Maria Nieves Gonzalez-Bravo  3 ,  Sergi Beltran  4  5 ,  Joaquin Dopazo  6 ,  Francisco Garcia-Garcia  6 ,  François Foulquier  7 ,  Gert Matthijs  8 ,  Philippa Mills  9 ,  Antonia Ribes  1 ,  Gustavo Egea  2 ,  Paz Briones  1 ,  Frederic Tort  1 ,  Marisa Girós  1
Affiliations
  • 1. Secció d'Errors Congènits del Metabolisme -IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBERER, Barcelona, Spain.
  • 2. Department Biomedicina, Universitat de Barcelona and Institut d'Investigacions Mèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • 3. Neonatologia Hospital Universitario de Canarias, La Laguna, Sta Cruz de Tenerife, Canarias, Spain.
  • 4. CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona, Spain.
  • 5. Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • 6. Centro de Investigación Príncipe Felipe (CIPF, CIBERER), c/Eduardo Primo Yufera 3, Valencia.
  • 7. Université de Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-, Lille, France.
  • 8. Centre for Human Genetics, KU Leuven, Leuven, Belgium.
  • 9. Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, United Kingdom.
PMID: 27862579 DOI: 10.1002/humu.23145
Abstract

Congenital disorders of glycosylation (CDG) are a heterogeneous and rapidly growing group of diseases caused by abnormal glycosylation of proteins and/or lipids. Mutations in genes involved in the homeostasis of the endoplasmic reticulum (ER), the Golgi apparatus (GA), and the vesicular trafficking from the ER to the ER-Golgi intermediate compartment (ERGIC) have been found to be associated with CDG. Here, we report a patient with defects in both N- and O-glycosylation combined with a delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex. TRAPPIII is implicated in the anterograde transport from the ER to the ERGIC as well as in the vesicle export from the GA. This report expands the spectrum of genetic alterations associated with CDG, providing new insights for the diagnosis and the understanding of the physiopathological mechanisms underlying glycosylation disorders.

Keywords
CDG; Golgi; TRAPPC11; endoplasmic reticulum; vesicle trafficking.