title: Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1.
abstract: 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.
authors.affiliation: Department of Pediatrics, University Hospitals Leuven, Herestraat 49, BE-3000 Leuven, Belgium.
authors.forename: Renate
authors.initials: R
authors.lastname: Zeevaert
authors.forename: François
authors.initials: F
authors.lastname: Foulquier
authors.forename: Boyan
authors.initials: B
authors.lastname: Dimitrov
authors.forename: Ellen
authors.initials: E
authors.lastname: Reynders
authors.forename: Rita
authors.initials: R
authors.lastname: Van Damme-Lombaerts
authors.forename: Emil
authors.initials: E
authors.lastname: Simeonov
authors.forename: Wim
authors.initials: W
authors.lastname: Annaert
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D001483:Base Sequence; D020126:Brefeldin A / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016368:Frameshift Mutation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C486489:COG1 protein, human; D020126:Brefeldin A