The rare mutation in the endosome-associated recycling protein gene is associated with human neural tube defects.

BACKGROUND

Tight control of endosome trafficking is essential for the generation of a normally patterned embryo. Recent studies have found that VPS50 is a key ingredient in EARP which is required for recycling of internalized TfRs to the cell surface and dense-core vesicle maturation. However, the role of in embryogenesis and human physiology are poorly understood.

RESULTS

We identified a rare missense heterozygous mutation (p. Gly169Val) in NTDs by high-throughput sequencing. In vitro functional analysis demonstrated that the p. Gly169Val was a loss-of-function mutation, delaying transferrin recycling and altering its interaction with VPS53. Using WISH during zebrafish embryogenesis, we demonstrated that gene was expressed throughout the early embryo, especially in the head. Abnormal body axis phenotypes were observed in those knock-down zebrafishes. Further rescue study in zebrafish suggested that the mutation displayed loss-of-function effects comparing with wild-type .

CONCLUSIONS

These findings thus demonstrated that the functional mutations in might contribute to neurodevelopmental disorder and highlighted the critical importance of function in cellular and organismal physiology.