Skip to main content

Integration of Glycomics, Genomics and Cell Biology in a study of Joubert Syndrome with OFD1 mutation

Wednesday, September 24, 2014 — Poster Session IV

10:00 a.m. –12:00 p.m.

FAES Academic Center




  • M.S. Kane
  • M. Davids
  • C. Adams
  • M. He
  • D.A. Doherty
  • W.A. Gahl
  • C.F. Boerkoel


The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) has begun an effort to integrate a multi-omics, agnostic approach to the study of rare and unknown diseases. The association of abnormal glycomics findings in patients with known diseases raises questions regarding the impact of glycosylation on disease pathogenesis or as a disease biomarker. One NIH UDP patient with abnormal glycosylation was found to have Joubert syndrome attributed to a genetic defect in OFD1. Analysis of N-linked glycosylation in two OFD1-Joubert patients' blood indicated below-average levels of galactosylation and sialylation, suggestive of a defect of N-linked glycosylation in the Golgi. Abnormal glycosylation was also seen in cultured primary fibroblasts, indicating that the abnormal glycosylation was not a nonspecific marker for illness. Therefore, we next transduced patient fibroblasts with a lentivirus expressing wild-type OFD1 to attempt to rescue the defect in glycosylation and observed normalization of the N-linked sialylated glycan profile. Abnormal lectin staining for sialylation was observed in primary fibroblasts and this also rescued with expression of wild-type OFD1 or culture of the primary fibroblasts in serum-free media. These observations are discussed in the context of their implications for how OFD1 mutations affect glycoprotein homeostasis.

back to top