Related Experiment Video
Updated: May 28, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Clinical Variability Within the PLOD2-Associated Phenotypic Continuum: Three Novel Variants in Four Patients from a
Elena S Merkuryeva1, Evgeniya A Melnik1, Vladimir M Kenis2
1Research Centre for Medical Genetics, 115522 Moscow, Russia.
Genes
|May 27, 2026
Summary
Bruck syndrome type 2, caused by PLOD2 gene variants, presents diverse bone fragility and skeletal deformities, even without congenital contractures. This expands understanding of PLOD2-associated disease and aids diagnosis in unexplained bone fragility cases.
Area of Science:
- Genetics
- Molecular Biology
- Skeletal Dysplasias
Background:
- Bruck syndrome type 2 (BS2) is an ultra-rare autosomal recessive disorder.
- It is part of the osteogenesis imperfecta (OI) spectrum.
- BS2 results from pathogenic variants in the PLOD2 gene, crucial for collagen cross-linking in bone.
Purpose of the Study:
- To delineate the clinical and molecular spectrum of PLOD2-associated disease.
- To identify novel variants and expand the understanding of genotype-phenotype correlations.
- To aid in the diagnosis of unexplained bone fragility.
Main Methods:
- Descriptive case series of four patients from three families.
- Clinical, radiological, and molecular evaluations.
- Next-generation sequencing, whole-exome sequencing, and Sanger sequencing for variant analysis.
Main Results:
- Four PLOD2 variants identified, three previously unreported.
- Clinical severity varied, with fractures occurring between 3 months and 4 years.
- Severe OI-like phenotype observed without congenital contractures; axial and pelvic involvement noted in older patients.
Conclusions:
- This series broadens the clinical presentation of PLOD2-associated disease.
- Severe bone fragility can occur without congenital contractures.
- PLOD2 should be considered in the differential diagnosis of unexplained bone fragility and skeletal deformities.
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