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Structural Variants in COL1A1 and COL1A2 in Osteogenesis Imperfecta
Dominyka Batkovskyte1, Diana Swolin-Eide2,3, Anna Hammarsjö1,4
1Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
American Journal of Medical Genetics. Part A
|November 8, 2024
Summary
Structural variants in type I collagen genes (COL1A1/COL1A2) cause Osteogenesis Imperfecta (OI). This study identified deletions and rearrangements in eight OI patients, highlighting the importance of gene dosage in OI.
Area of Science:
- Genetics
- Molecular Biology
- Orthopedics
Background:
- Osteogenesis Imperfecta (OI) is a skeletal dysplasia characterized by bone fragility.
- Most OI cases result from variants in type I collagen genes (COL1A1, COL1A2).
- Structural gene abnormalities are less common causes of OI.
Purpose of the Study:
- To investigate structural variants in COL1A1 and COL1A2 in Swedish OI patients.
- To analyze the clinical and genetic variability of OI caused by these variants.
- To emphasize the role of gene dosage abnormalities in OI.
Main Methods:
- Genetic analysis of eight Swedish patients from five families with OI.
- Identification of structural variants including deletions, duplications, and complex rearrangements in COL1A1 and COL1A2.
- Correlation of genetic findings with OI phenotypes.
Main Results:
- Eight patients presented with OI due to structural variants in COL1A1 or COL1A2.
- Identified were a complex rearrangement in COL1A2, whole gene deletions in COL1A1, intragenic deletions in COL1A2, and a large de novo deletion encompassing COL1A1.
- These variants led to reduced gene expression or haploinsufficiency, correlating with OI phenotypes.
Conclusions:
- Structural variants and gene dosage abnormalities in type I collagen genes are significant causes of OI.
- The study expands the understanding of genetic heterogeneity in OI.
- Investigating gene dosage is crucial for diagnosing OI patients with suspected collagen gene defects.
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