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CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking

The transmembrane domain recognition complex (TRC) pathway is required for the insertion of C-terminal tail-anchored (TA) proteins into the lipid bilayer of specific intracellular organelles such as the endoplasmic reticulum (ER) membrane. In order to facilitate correct insertion, the recognition complex (consisting of BAG6, GET4 and UBL4A) must first bind to TA proteins and then to GET3 (TRC40, ASNA1) which chaperones the protein to the ER membrane. Subsequently, GET1 (WRB) and CAML form a receptor which enables integration of the TA protein within the lipid bilayer. We report an individual with the homozygous c.633 + 4A > G splice variant in CAMLG, encoding CAML. This variant leads to aberrant splicing and lack of functional protein in patient-derived fibroblasts.