TMEM165 Deficiency Causes a Congenital Disorder of Glycosylation
| Autor: | Pierre Morsomme, Mustapha Amyere, Valerie Race, Dominique Legrand, W. Annaert, Hudson H. Freeze, Jaak Jaeken, Neil R. M. Buist, Didier Demaegd, Riet Bammens, Emile Van Schaftingen, Els Schollen, Renate Zeevaert, Claire Rosnoblet, David Cheillan, Gert Matthijs, François Foulquier, Miikka Vikkula, Willy Morelle, Nathalie Guffon |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Glycosylation Adolescent Golgi Apparatus Dwarfism Biology medicine.disease_cause Antiporters Article 03 medical and health sciences chemistry.chemical_compound symbols.namesake 0302 clinical medicine Congenital Disorders of Glycosylation medicine Genetics Missense mutation Humans Genetics(clinical) Child Cation Transport Proteins Genetics (clinical) Cells Cultured 030304 developmental biology Skin chemistry.chemical_classification 0303 health sciences Mutation HEK 293 cells Infant Newborn Infant Membrane Proteins Golgi apparatus Fibroblasts medicine.disease Pedigree Ion homeostasis chemistry Child Preschool symbols Female Glycoprotein Congenital disorder of glycosylation 030217 neurology & neurosurgery |
| Zdroj: | The American Journal of Human Genetics. 91(1):15-26 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2012.05.002 |
| Popis: | Protein glycosylation is a complex process that depends not only on the activities of several enzymes and transporters but also on a subtle balance between vesicular Golgi trafficking, compartmental pH, and ion homeostasis. Through a combination of autozygosity mapping and expression analysis in two siblings with an abnormal serum-transferrin isoelectric focusing test (type 2) and a peculiar skeletal phenotype with epiphyseal, metaphyseal, and diaphyseal dysplasia, we identified TMEM165 (also named TPARL) as a gene involved in congenital disorders of glycosylation (CDG). The affected individuals are homozygous for a deep intronic splice mutation in TMEM165. In our cohort of unsolved CDG-II cases, we found another individual with the same mutation and two unrelated individuals with missense mutations in TMEM165. TMEM165 encodes a putative transmembrane 324 amino acid protein whose cellular functions are unknown. Using a siRNA strategy, we showed that TMEM165 deficiency causes Golgi glycosylation defects in HEK cells. |
| Databáze: | OpenAIRE |
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