ABSTRACT
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.
