TMEM165 Deficiency Causes a Congenital Disorder of Glycosylation

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2012 Jun 12

PMID 22683087

Citations 104

Authors

Francois Foulquier

Mustapha Amyere

Jaak Jaeken

Renate Zeevaert

Els Schollen

Valerie Race

Riet Bammens

Willy Morelle

Claire Rosnoblet

Dominique Legrand

Didier Demaegd

Neil Buist

David Cheillan

Nathalie Guffon

Pierre Morsomme

Willem Annaert

Hudson H Freeze

Emile Van Schaftingen

Miikka Vikkula

Gert Matthijs

Affiliations

Soon will be listed here.

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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