TY - JOUR
T1 - A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia
AU - Morava, Eva
AU - Zeevaert, Renate
AU - Korsch, Eckhard
AU - Huijben, Karin
AU - Wopereis, Suzan
AU - Matthijs, Gert
AU - Keymolen, Kathelijn
AU - Lefeber, Dirk J.
AU - De Meirleir, Linda
AU - Wevers, Ron A.
N1 - Funding Information:
The work was supported by the European Commission (FPG, contract No 512131 (EUROGLYCANET)). Renate Zeevaert is a PhD fellow for the FWO, Vlaanderen. Further special thanks for the unpublished information provided by Leo Spaapen, and to Monty Krieger, Daniel Ungar and Vladimir Lupashin for providing antibodies.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34249678544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249678544&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201813
DO - 10.1038/sj.ejhg.5201813
M3 - Article
C2 - 17356545
AN - SCOPUS:34249678544
SN - 1018-4813
VL - 15
SP - 638
EP - 645
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -