Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes

Scientific Reports
Xin ChenJie Du

Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL), which is characterized by ectopic bone formation in the spinal ligaments, can cause spinal-cord compression. To date, at least 11 susceptibility genes have been genetically linked to OPLL. In order to identify potential deleterious alleles in these OPLL-associated genes, we designed a capture array encompassing all coding regions of the target genes for next-generation sequencing (NGS) in a cohort of 55 unrelated patients with OPLL. By bioinformatics analyses, we successfully identified three novel and five extremely rare variants (MAF < 0.005). These variants were predicted to be deleterious by commonly used various algorithms, thereby resulting in missense mutations in four OPLL-associated genes (i.e., COL6A1, COL11A2, FGFR1, and BMP2). Furthermore, potential effects of the patient with p.Q89E of BMP2 were confirmed by a markedly increased BMP2 level in peripheral blood samples. Notably, seven of the variants were found to be associated with the patients with continuous subtype changes by cervical spinal radiological analyses. Taken together, our findings revealed for the first time that deleterious coding variants of the four OPLL-associated genes are p...Continue Reading

References

Jul 12, 2019·Journal of Orthopaedic Surgery and Research·Peng WangShibao Lu
Mar 14, 2019·International Journal of Molecular Medicine·Peng WangShibao Lu

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Related Concepts

FGFR1
Fibroblast Growth Factor Receptor 1
Ligaments
Genes
Peripheral Blood
Procollagen Type VI
Pathogenic Organism
FGFR1 wt Allele
BMP2 gene
Candidate Disease Gene

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