Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by Cartilage-associated Protein (CRTAP) Variants
Authors' conclusion
The novel c.621 + 1G > A mutation in CRTAP expands the genotypic spectrum of type VII OI. Biallelic mutations of c.621 + 1G > A and c.1153-3C > G in CRTAP can lead to reduced CRTAP mRNA and deficient CRTAP protein in osteoblasts, which reduces 3-hydroxylation in Pro986 of the α1 chain of type I collagen and impairs bone formation, thus contributing to severe OI type VII.
Study context
- Population
- Two nonconsanguineous families with CRTAP mutations (osteogenesis imperfecta (OI) type VII)2 families
- Comparison
- OI patient with CRTAP mutations vs normal control
- OI patientn = 1
- Outcome
- CRTAP expression, collagen prolyl 3-hydroxylation and bone formation in a patient with biallelic c.621 + 1G > A and c.1153-3C > G CRTAP mutations vs a normal control
Methodological detailsgenetic analysis, functional study on bone specimens
- Genetic analysis
- Functional study on bone specimens
Main finding
As reported in the abstract
- c.621 + 1G > A: novel mutation impairing mRNA transcription, leading to a truncated CRTAP protein
- CRTAP mRNA and protein levels in osteoblasts significantly decreased vs normal control
- Osteoid volume and osteoblast numbers markedly reduced vs normal control
- Significantly reduced prolyl 3-hydroxylation at Pro986 in the α1 chain of type I collagen and invisible active bone formation
Original publication
Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants. J Clin Endocrinol Metab. Published 12 January 2024. doi:10.
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