Abstract
Abstract
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.
Funder
National Institute of Health
The University of Tokyo
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology, Diabetes and Metabolism
Cited by
3 articles.
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