Unveiling the genetic variation of severe continuous/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis

Lee, Young Moo; Kim, Ki Tae; Kim, Chi Heon; Lee, Eun Young; Lee, Sang Gu; Seo, Myung Eui; Kim, Ju Han; Chung, Chun Kee

doi:10.1016/j.spinee.2021.07.005

Cited by 9 publications

(13 citation statements)

References 48 publications

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“…The authors proposed that the causal variations of genetic OPLL might be auto-/local inflammation-related genes such as NLRP1, SSH2, and CYP4B1. 29 Previous genetic studies also suggested that the inflammatory response were related to OPLL. 31,32 In a clinical study, serum level of C-reactive protein (CRP) as well-known inflammatory marker was higher in the OPLL group than in the control group, and the group with progression of OPLL showed much higher CRP levels than the group with nonprogression of OPLL.…”

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

“…28 However, the RSPO2 gene did not show a significant difference in other researchers' studies, including a whole-exome sequencing (WES) study. 29 Two WES studies that used the most up-to-date and precise methods to discover causal variations were published by researchers from Korea and China. 29,30 One paper included 28 patients with OPLL (67%, continuous/mixed type) and suggested that variants of the PTCH1 and COL17A1 genes might contribute to the development of OPLL.…”

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

“…29 Two WES studies that used the most up-to-date and precise methods to discover causal variations were published by researchers from Korea and China. 29,30 One paper included 28 patients with OPLL (67%, continuous/mixed type) and suggested that variants of the PTCH1 and COL17A1 genes might contribute to the development of OPLL. 30 PTCH1 is related to basal cell carcinoma, and no precise relationship was found between the results of the study and clinical findings.…”

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

“…The other WES study included 74 OPLL patients (100% with the continuous/mixed type and a ≥ 40% occupying ratio) and 26 controls and was published this year. 29 A characteristic of this paper is that the patients group was selected very precisely and that it probably included more patients with OPLL caused by genetic diseases than other previous studies. The authors proposed that the causal variations of genetic OPLL might be auto-/local inflammation-related genes such as NLRP1, SSH2, and CYP4B1.…”

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

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Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review

et al. 2022

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Despite numerous studies, the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unclear. Previous genetic studies proposed variations in genes related to bone and collagen as a cause of OPLL. It is unclear whether the upregulations of those genes are the cause of OPLL or an intermediate result of endochondral ossification process. Causal variations may be in the inflammation-related genes supported by clinical and updated genomic studies. OPLL demonstrates features of genetic diseases but can also be induced by mechanical stress by itself. OPLL may be a combination of various diseases that share ossification as a common pathway and can be divided into genetic and idiopathic. The phenotype of OPLL can be divided into continuous (including mixed) and segmental (including localized) based on the histopathology, prognosis, and appearance. Continuous OPLL shows substantial overexpression of osteoblast-specific genes, frequent upper cervical involvement, common progression, and need for surgery, whereas segmental OPLL shows moderate-to-high expression of these genes and is often clinically silent. Genetic OPLL seems to share clinical features with the continuous type, while idiopathic OPLL shares features with the segmental type. Further genomic studies are needed to elucidate the relationship between genetic OPLL and phenotype of OPLL.

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Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

Section: Pathogenesis Ii: Review Of Genomic Variation Discovery Studiesmentioning

confidence: 99%

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Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review

et al. 2022

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“…OPLL is morphologically classi ed into localized, segmental, continuous and mixed types [7]. Localized OPLL refers to an ectopic bone formation in the disc space or extending to the posterior border of the vertebral body [8].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Anterior Cervical Discectomy and Fusion and Anterior Cervical Corpectomy and Fusion in Localized Ossification of the Posterior Longitudinal Ligament

Chen

Wang

Zhou

et al. 2022

Preprint

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The retrospective study was conducted to compare the efficacy of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) for localized ossification of the posterior longitudinal ligament (OPLL) by evaluating clinical and radiologic outcomes. We reviewed 151 patients to assess the effects of treatment for localized OPLL. Perioperative parameters, such as blood loss, operation time and complications, were recorded. Radiologic outcomes, such as the occupying ratio (OR), fusion status, cervical lordosis angle, segmental angle, segmental height, T1 slope, and C2–C7 sagittal vertical axis (SVA), were assessed. Clinical indices, such as the JOA scores and VAS scores, were investigated to compare the two surgical options. There were no significant differences in the JOA scores or VAS scores between the two groups (P > 0.05). The operation time, volume of blood loss and incidence of dysphagia were significantly less in the ACDF group than in the ACCF group(P < 0.05). In addition, cervical lordosis, segmental angle and segmental height were significantly different from their preoperative evaluations. Both groups had significantly improved T1 slopes. Moreover, C2–C7 SVA was significantly increased at the last follow-up. No adjacent segment degenerated in the ACDF group. The degeneration of the ACCF group was 4.1%. The incidence of CSF leaks was 7.8% in the ACDF group and 13.5% in the ACCF group. All the patients ultimately achieved successful fusion. Although both options achieved satisfactory primary clinical and radiographic efficacies, ACDF was associated with a shorter surgical procedure, less volume of intraoperative blood loss, better radiologic outcomes and lower incidence of dysphagia than ACCF.

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Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments

Kato,

Braddock,

Ito

2023

Curr Osteoporos Rep

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Purpose of Review The study aims to provide updated information on the genetic factors associated with the diagnoses ‘Diffuse Idiopathic Skeletal Hyperostosis’ (DISH), ‘Ossification of the Posterior Longitudinal Ligament’ (OPLL), and in patients with spinal ligament ossification. Recent Findings Recent studies have advanced our knowledge of genetic factors associated with DISH, OPLL, and other spinal ossification (ossification of the anterior longitudinal ligament [OALL] and the yellow ligament [OYL]). Several case studies of individuals afflicted with monogenic disorders, such as X-linked hypophosphatemia (XLH), demonstrate the strong association of fibroblast growth factor 23-related hypophosphatemia with OPLL, suggesting that pathogenic variants in PHEX, ENPP1, and DMP1 are associated with FGF23-phosphate wasting phenotype and strong genetic factors placing patients at risk for OPLL. Moreover, emerging evidence demonstrates that heterozygous and compound heterozygous ENPP1 pathogenic variants inducing ‘Autosomal Recessive Hypophosphatemic Rickets Type 2’ (ARHR2) also place patients at risk for DISH and OPLL, possibly due to the loss of inhibitory plasma pyrophosphate (PPi) which suppresses ectopic calcification and enthesis mineralization. Summary Our findings emphasize the importance of genetic and plasma biomarker screening in the clinical evaluation of DISH and OPLL patients, with plasma PPi constituting an important new biomarker for the identification of DISH and OPLL patients whose disease course may be responsive to ENPP1 enzyme therapy, now in clinical trials for rare calcification disorders.

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Unveiling the genetic variation of severe continuous/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis

Cited by 9 publications

References 48 publications

Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review

Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review

Comparison of Anterior Cervical Discectomy and Fusion and Anterior Cervical Corpectomy and Fusion in Localized Ossification of the Posterior Longitudinal Ligament

Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments

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