title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
abstract: We describe the clinical and biochemical characteristics in three patients from two different families diagnosed with Congenital Disorder of Glycosylation type IIe owing to a defect in Conserved Oligomeric Golgi complex (COG)7; one of the eight subunits of the COG. The siblings and an unrelated single child of consanguineous parents presented with growth retardation, progressive, severe microcephaly, hypotonia, adducted thumbs, feeding problems by gastrointestinal pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin and episodes of extreme hyperthermia. A combined disorder in the biosynthesis of N- and O-linked glycosylation with hyposialylation was detected. Western blot analysis showed a severe reduction in the COG5 and 7 subunits of the COG. A homozygous, intronic splice site mutation (c.169+4A>C) of the COG7 gene was identified in all patients. The phenotype is similar to that previously described in two patients of North African ethnicity with the same mutation, except for the lack of skeletal anomalies and only a mild liver involvement in our patients. We suggest performing protein glycosylation studies and Western blot for the different COG subunits in patients with progressive microcephaly, growth retardation, hypotonia, adducted thumbs and cardiac defects, especially in association with skin anomalies or episodes of hyperthermia. The presence of the characteristic phenotype might warrant direct DNA analysis.
authors.affiliation: Department of Pediatrics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. e.morava@cukz.umcn.nl
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
authors.forename: Renate
authors.initials: R
authors.lastname: Zeevaert
authors.forename: Eckhard
authors.initials: E
authors.lastname: Korsch
authors.forename: Karin
authors.initials: K
authors.lastname: Huijben
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Keymolen
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Lefeber
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D053305:Apolipoprotein C-III / Q000378:metabolism; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics*; D005183:Failure to Thrive; D017809:Fatal Outcome; D005260:Female; D006031:Glycosylation; D006056:Golgi Apparatus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007525:Isoelectric Focusing; D008297:Male; D008831:Microcephaly / Q000235:genetics; D009154:Mutation; D013577:Syndrome; D013933:Thumb / Q000002:abnormalities; D014168:Transferrin / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D053305:Apolipoprotein C-III; C512294:COG7 protein, human; D014168:Transferrin