TMEM165 Deficiency Causes a Congenital Disorder of Glycosylation.
(2012) American Journal of Human Genetics — Vol. 91, n° 1, p. 15-26 (2012)
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- Abstract
- 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.
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Foulquier, F., Amyere, M., Jaeken, J., Zeevaert, R., Schollen, E., Race, V., Bammens, R., Morelle, W., Rosnoblet, C., Legrand, D., Demaegd, D., Buist, N., Cheillan, D., Guffon, N., Morsomme, P., Annaert, W., Freeze, H. H., Van Schaftingen, E., Vikkula, M., & Matthijs, G. (2012). TMEM165 Deficiency Causes a Congenital Disorder of Glycosylation. American Journal of Human Genetics, 91(1), 15-26. https://doi.org/10.1016/j.ajhg.2012.05.002 (Original work published 2012)