PUBLICATION
A novel de novo mutation in COL1A1 leading to osteogenesis imperfecta confirmed by zebrafish model
- Authors
- Huang, H., Liu, J., Zhang, G.
- ID
- ZDB-PUB-210312-15
- Date
- 2021
- Source
- Clinica chimica acta; international journal of clinical chemistry 517: 133-138 (Journal)
- Registered Authors
- Keywords
- COL1A1, Osteogenesis imperfecta, Zebrafish, panel
- MeSH Terms
-
- Animals
- Collagen
- Collagen Type I/genetics
- Female
- Humans
- Mutation
- Osteogenesis Imperfecta*/diagnostic imaging
- Osteogenesis Imperfecta*/genetics
- Phenotype
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 33705765 Full text @ Clin. Chim. Acta
Citation
Huang, H., Liu, J., Zhang, G. (2021) A novel de novo mutation in COL1A1 leading to osteogenesis imperfecta confirmed by zebrafish model. Clinica chimica acta; international journal of clinical chemistry. 517:133-138.
Abstract
Purpose Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders. Mutations in two genes, collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 1 chain (COL1A2), which encode the pro-a1 (I) and pro-a2 (I) chains of type I collagen, respectively, the most abundant form of collagen in the human body, cause most cases of OI.
Methods In this study, we used panel-based next-generation sequencing for prenatal diagnosis of a fetus whose ultrasound images suggested OI. A de novo mutation in COL1A1 gene was suspected to cause the phenotype. To validate the effect of this mutation in a zebrafish model, we constructed a plasmid containing the corresponding mutation in the zebrafish gene col1a1a (c.1744 G>A), and overexpressed the mutant protein in zebrafish larvae.
Results We identified a novel COL1A1 mutation (c.1822 G>A; p.Gly608Ser) in the fetus but not in her parents by an skeletal dysplasias panel. Bioinformatic analysis showed that the affected residue (p.Gly608) is highly conserved from zebrafish to humans. In contrast to larvae expressing wild-type (WT) col1a1a and enhanced green fluorescent protein (EGFP), col1a1a mutation-expressing larvae showed significant spinal curvature and embryonic lethality, mimicking the phenotype of human OI.
Conclusions Our study revealed the pathogenicity of a de novo mutation, c.1822 G>A, in human COL1A1, which expands the mutation spectrum of OI.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping