Research on Congenital Disorders of Glycosylation (CDGs)

GGC’s Research Division actively studies a group of inherited diseases called the Congenital Disorders of Glycosylation or CDG.  These rare diseases are caused by defects in enzymes and proteins responsible for adding sugars onto proteins and lipids, a process known as glycosylation.  When proteins or lipids in the cell are abnormally glycosylated, their biological functions can become impaired.  Patients with CDG have multisystem complications reflecting the central importance of glycosylation to the development and maintenance of most major organ systems in the human body.  Once thought to be very rare, more and more CDG types that affect the different glycosylation pathways in the cell are being identified each year.

The steps in the synthesis of the lipid-linked sugar precursor for N-linked glycosylation- a process that occurs on both sides of the endoplasmic reticulum.  Nearly all the genes in this pathway are now represented by CDG. 

Images of wild type and pmm2 mutant zebrafish cartilage that is marked by GFP.  The pmm2 mutant cartilage cells or chondrocytes are more disorganized than wild type. Large vacuoles are also observed in the chondrocytes of the pmm2 mutant zebrafish.  GGC researchers are actively studying the mechanisms that cause the vacuoles and abnormal cartilage formation.

GGC researchers are studying CDG on numerous levels, with a major focus on understanding the pathogenesis of the most common CDG, PMM2-CDG.  Their team is investigating how abnormal glycosylation causes the tissue-specific symptoms of this and other related CDG. They are using this information to explore novel treatments in partnership with multiple academic collaborators.  The Division is taking advantage of novel zebrafish models to unravel the complex nature of CDG and identify the key proteins and pathways involved in the disease process.  GGC researchers are working to identify the transcriptome and protein changes that are most sensitive to global defects in glycosylation.  Much of this work is done in collaboration with other research groups around the country, including the following projects:

  • Investigating the metabolic consequences of PMM2-CDG and their impact on disease pathogenesis (in collaboration with Dr. Eva Morava at the Mayo Clinic)
  • Defining the functional impact of SLC35A2 variants (in collaboration with Som Mukhopadhyay at UT-Austin and Alicia Renck at Stanford)

Meet Makayla Gunn

Makayla was diagnosed with Rett Syndrome in April of 2015 at the age of two. At about 18 months, we noticed she had started some repetitive hand motions, and her pediatrician was a little concerned that she did not have many words. She had learned some sign language, and was saying ‘mama’ and ‘dada’, but that was it. Then she suddenly stopped all of that. At her 2 year old check-up, the pediatrician referred us to BabyNet, SC’s early interve...

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