PUBLICATION
Functional variants of hepatocyte growth factor identified in patients with adolescent idiopathic scoliosis
- Authors
- Meng, Y., Ma, J., Lin, T., Jiang, H., Wang, C., Yang, F., Zhou, X.
- ID
- ZDB-PUB-190601-19
- Date
- 2019
- Source
- Journal of cellular biochemistry 120(10): 18236-18245 (Journal)
- Registered Authors
- Ma, Jun
- Keywords
- adolescent idiopathic scoliosis, autosomal dominant inheritance, hepatocyte growth factor, whole-genome sequencing
- MeSH Terms
-
- Adolescent
- Animals
- Asian People/genetics
- Base Sequence
- Body Patterning/genetics
- China
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Female
- Gene Knockdown Techniques
- Genetic Predisposition to Disease/ethnology
- Genetic Predisposition to Disease/genetics*
- HEK293 Cells
- Hepatocyte Growth Factor/genetics*
- Humans
- Male
- Mutation, Missense*
- Pedigree
- Scoliosis/ethnology
- Scoliosis/genetics*
- Whole Genome Sequencing/methods
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 31148267 Full text @ J. Cell. Biochem.
Citation
Meng, Y., Ma, J., Lin, T., Jiang, H., Wang, C., Yang, F., Zhou, X. (2019) Functional variants of hepatocyte growth factor identified in patients with adolescent idiopathic scoliosis. Journal of cellular biochemistry. 120(10):18236-18245.
Abstract
The genetic etiology of adolescent idiopathic scoliosis (AIS) remains obscure. Whole-genome sequencing was performed in four members of one family. Then, we performed a rigorous computational analysis to determine the deleterious effects of the identified variants. Furthermore, the structural differences between the native hepatocyte growth factor (HGF) protein and a protein encoded by an HGF variant containing one mutation (p.T596M) were analyzed using molecular dynamic stimulation. A novel heterozygous mutation (p.T596M) within the HGF gene was identified and found to cosegregate with scoliosis phenotypes in three affected family members. Subsequent modeling and structure-based analyses supported the theory that this mutation is functionally deleterious. Functional analyses demonstrated that the HGF p.T596 M mutation changed the ability of the HGF protein to be secreted and impaired migration and invasion in HEK293T cells. Furthermore, an HGF knockdown zebrafish model exhibited a curly tailed phenotype. Mutation in HGF is associated with an autosomal dominant pattern of inheritance of AIS. This finding increases our understanding of the genetic heterogeneity of AIS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping