Genetic variants and phenotypic analysis in patients with ossification of the posterior longitudinal ligament
Objective:To identify potential pathogenic factors in patients with ossification of the posterior longitudinal ligament(OPLL)through whole exome sequencing(WES)Methods:Genomic DNA was extracted from the peripheral blood of 93 OPLL patients admitted from January 2017 to December 2019 for WES and bioinformatics analysis were performed to identify gene variants associated with OPLL.Results:Two missense variants in ENPP1 were identified in two OPLL patients.Case 1 carried a heterozygous variant c.T802C(p.Tyr268His),while Case 2 carried a heterozygous variant c.T253C(p.Cys85Arg)and a heterozygous variant c.T802C(p.Tyr268His).Both variant sites are highly conserved across different species.Several in silico tools predicted the two variants to be damaging or possibly damaging.Phenotypic analysis revealed that both patients had cervical and thoracic OPLL as well as thoracic ossification of ligamentum flavum.Case 2 had a serum phosphate level at the lower limit of normal,with a serum alkaline phosphatase level above the normal value.Conclusions:Variants of ENPP1 may contribute to the pathogenesis of OPLL in these two patients.This study enriches the spectrum of ENPP1 gene variants,and provides molecular diagnostic evidence for future application of novel therapeutic strategies in OPLL patients.
Ossification of Posterior Longitudinal LigamentGenetic VariantsWhole Exome SequencingEctonucleotide Pyrophosphatase/Phosphodiesterase 1
NETL
NSTL
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