PUBLICATION
NANS-mediated synthesis of sialic acid is required for brain and skeletal development
- Authors
- van Karnebeek, C.D., Bonafé, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Van Allen, M.I., Rossi, A., Engelke, U.F., Kluijtmans, L.A., van der Heeft, E., Renkema, H., de Brouwer, A., Huijben, K., Zijlstra, F., Heisse, T., Boltje, T., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., Superti-Furga, A.
- ID
- ZDB-PUB-160524-3
- Date
- 2016
- Source
- Nature Genetics 48(7): 777-84 (Journal)
- Registered Authors
- Keywords
- Clinical genetics, Experimental models of disease, Genetics research
- MeSH Terms
-
- Developmental Disabilities/genetics
- Developmental Disabilities/metabolism
- Developmental Disabilities/pathology*
- Animals
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Age of Onset
- Child, Preschool
- Male
- Humans
- Mutation/genetics*
- Infant, Newborn
- Brain/embryology*
- Brain/metabolism
- Brain/pathology
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/pathology
- Sialic Acids/metabolism*
- Metabolism, Inborn Errors/genetics
- Metabolism, Inborn Errors/metabolism
- Metabolism, Inborn Errors/pathology
- Oxo-Acid-Lyases/genetics*
- Adult
- Infant
- Female
- Fibroblasts/metabolism
- Fibroblasts/pathology
- Bone Diseases, Developmental/genetics
- Bone Diseases, Developmental/metabolism
- Bone Diseases, Developmental/pathology*
- PubMed
- 27213289 Full text @ Nat. Genet.
- CTD
- 27213289
Citation
van Karnebeek, C.D., Bonafé, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Van Allen, M.I., Rossi, A., Engelke, U.F., Kluijtmans, L.A., van der Heeft, E., Renkema, H., de Brouwer, A., Huijben, K., Zijlstra, F., Heisse, T., Boltje, T., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., Superti-Furga, A. (2016) NANS-mediated synthesis of sialic acid is required for brain and skeletal development. Nature Genetics. 48(7):777-84.
Abstract
We identified biallelic mutations in NANS, the gene encoding the synthase for N-acetylneuraminic acid (NeuNAc; sialic acid), in nine individuals with infantile-onset severe developmental delay and skeletal dysplasia. Patient body fluids showed an elevation in N-acetyl-D-mannosamine levels, and patient-derived fibroblasts had reduced NANS activity and were unable to incorporate sialic acid precursors into sialylated glycoproteins. Knockdown of nansa in zebrafish embryos resulted in abnormal skeletal development, and exogenously added sialic acid partially rescued the skeletal phenotype. Thus, NANS-mediated synthesis of sialic acid is required for early brain development and skeletal growth. Normal sialylation of plasma proteins was observed in spite of NANS deficiency. Exploration of endogenous synthesis, nutritional absorption, and rescue pathways for sialic acid in different tissues and developmental phases is warranted to design therapeutic strategies to counteract NANS deficiency and to shed light on sialic acid metabolism and its implications for human nutrition.
Errata / Notes
This article is corrected by ZDB-PUB-220906-74 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping