Human Molecular Genetics vol:18 issue:3 pages:517-524
We describe two patients with a cerebrocostomandibular-like syndrome and a novel mutation in conserved oligomeric Golgi (COG) subunit 1, one of the subunits of the conserved oligomeric Golgi complex. This hetero-octameric protein complex is involved in retrograde vesicular trafficking and glycosylation. We identified in both patients an intronic mutation, c.1070+5G>A, that disrupts a splice donor site and leads to skipping of exon 6, a frameshift and a premature stopcodon in exon 7. Real-time reverse transcriptase polymerase chain reaction showed in the first patient only 3% of normal transcript when compared with control. A delay in retrograde trafficking could be demonstrated by Brefeldin A treatment of this patient's fibroblasts. The costovertebral dysplasia of the two patients has been described in cerebrocostomandibular syndrome (CCMS), but also in cerebrofaciothoracic dysplasia and spondylocostal dysostosis. CCMS itself is heterogeneous because both autosomal dominant and autosomal recessive inheritance has been described. We anticipate further genetic heterogeneity because no mutations in COG1 were found in two additional patients with a CCMS.