Identification of the first COG-CDG patient of Indian origin.

Mutations in the Conserved Oligomeric Golgi (COG) complex give rise to type II congenital disorders of glycosylation (CDG). Thus far, mutations have been identified in 6 of the 8 COG subunits. Here we present data identifying a previously reported CDG-IIx case from Singapore as a new COG4 patient with 2 novel mutations leading to p.E233X and p.L773R; with p.E233X being a de novo mutation. As a result, COG4 protein expression was dramatically reduced, while expression of the other subunits remained unaffected. Analysis of serum N-glycans revealed deficiencies in both sialylation and galactosylation. Furthermore, patient fibroblasts have impaired O-glycosylation. Importantly, patient fibroblasts exhibited a delay in Brefeldin A (BFA) induced retrograde transport, a common characteristic seen in COG deficiencies.

[1]  Thierry Hennet,et al.  Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol‐linked oligosaccharides , 2009, Human mutation.

[2]  C. Thiel,et al.  Fatal outcome due to deficiency of subunit 6 of the conserved oligomeric Golgi complex leading to a new type of congenital disorders of glycosylation. , 2010, Human molecular genetics.

[3]  I. Brockhausen.  Chapter 5 Biosynthesis 3. Biosynthesis of O-Glycans of the N-Acetylgalactosamine-α-Ser/Thr Linkage Type , 1995 .

[4]  N. Callewaert,et al.  Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[5]  O. Bohorov,et al.  Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder , 2004, Nature Medicine.

[6]  Hudson H. Freeze,et al.  Genetic defects in the human glycome , 2006, Nature Reviews Genetics.

[7]  M. Krieger,et al.  Subunit Architecture of the Conserved Oligomeric Golgi Complex* , 2005, Journal of Biological Chemistry.

[8]  H. Freeze,et al.  Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIx. , 2005, The Journal of pediatrics.

[9]  M. Krieger,et al.  A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. , 2007, Human molecular genetics.

[10]  J. Denecke,et al.  Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies , 2003, European Journal of Pediatrics.

[11]  W. Annaert,et al.  Golgi function and dysfunction in the first COG4-deficient CDG type II patient , 2009, Human molecular genetics.

[12]  Matthias Baumgartner,et al.  Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation. , 2009, Human molecular genetics.

[13]  S. Kornfeld,et al.  COG-7-deficient Human Fibroblasts Exhibit Altered Recycling of Golgi Proteins. , 2006, Molecular biology of the cell.

[14]  H. Freeze,et al.  Molecular and clinical characterization of a Moroccan Cog7 deficient patient. , 2007, Molecular genetics and metabolism.

[15]  D. Dykxhoorn,et al.  Genetic Analysis of the Subunit Organization and Function of the Conserved Oligomeric Golgi (COG) Complex , 2005, Journal of Biological Chemistry.

[16]  H. Freeze,et al.  COG8 deficiency causes new congenital disorder of glycosylation type IIh. , 2007, Human molecular genetics.

[17]  Gert Matthijs,et al.  Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation. , 2008, Molecular genetics and metabolism.