Objective:　To　identify　the　likely　causal　mutation　that　results　in　disc　degeneration　in　a　pedigree　with　a　high　incidence　of　disc　degeneration.　Materials　and　Methods:　A　large　pedigree　with　a　high　incidence　of　disc　degeneration　was　recruited　for　this　study.　Exome　sequencing　was　completed　on　four　family　members　with　disc　degeneration　to　screen　for　potential　causal　gene　variants.　Detected　variants　were　filtered　against　the　1000　Genomes　Project,　the　Short　Genetic　Variations　database　(dbSNP),　and　the　Beijing　Genomics　Institute　(BGI)　in-house　database.　After　removing　synonymous　variants,　Sanger　sequencing　was　used　to　verify　the　lack　of　the　candidate　single　nucleotide　polymorphism　(SNP)　in　five　healthy　subjects　of　the　study　family.　Results:　We　identified　a　novel　SNP　variant,　Chr12:g.53494591T＞C.　c.T430C　(p.S144P)　in　the　insulin-like　growth　factor　binding　protein-6　(IGFBP6)　gene.　This　variant　was　shared　by　all　four　affected　family　members,　but　not　by　five　unaffected　members　in　the　same　pedigree.　Furthermore,　this　variant　was　not　detected　in　200　unrelated　healthy　people.　Conclusions:　The　c.T430C　(p.S144P)　variant　of　IGFBP6　was　identified　as　the　likely　causal　variant　associated　with　increased　risk　of　familial　disc　degeneration　in　the　studied　pedigree.