Autosomal recessive variants in TRAPPC9 have for the first time been linked to a congenital glycosylation defect. Researchers identified biallelic missense variants of TRAPPC9 in three patients with a novel syndromic phenotype of intellectual disability, dysmorphic features and an N-glycosylation defect.

TRAPPC9 variants causing a deficiency in the encoded protein, trafficking protein particle complex subunit 9, have previously been described as underlying intellectual disability in isolated form or as part of an autosomal recessive syndrome characterized also by obesity, brain malformations, facial dysmorphism and other features. TRAPPC9, a subunit of the TRAPPII complex, is involved in important intracellular transport processes and also in the NF-kappaB signalling pathway, which is essential in neuronal development. The study’s findings from functional and biochemical cell model investigations involving patient fibroblasts suggest a previously unknown role of TRAPPC9 related to glycosylation. In this complex chain of biochemical reactions, sugar chains are formed that adhere to proteins. The resulting glycoproteins are needed for vital processes and functioning of all tissues and organs in the human body.

The results of the study have been published in Genetics in Medicine.