IGFBP6 – Intervertebral Disk Degenerative Disorder

A recent study (PMID:28829625) described a large disc degeneration pedigree in which exome sequencing identified a novel IGFBP6 variant that segregated with disease. In this pedigree, four individuals exhibited intervertebral disk degeneration while five unaffected family members did not carry the variant. The reported variant, c.430T>C (p.Ser144Pro), was absent in 200 unrelated healthy controls, supporting its pathogenic potential. The evidence comes exclusively from this familial case series and thus represents a preliminary, though promising, observation for diagnostic decision‑making in familial disc degeneration.

The genetic evidence for IGFBP6 in intervertebral disk degenerative disorder points to an autosomal dominant mode of inheritance, given the strong co‑segregation of the variant with affected status within the pedigree. However, no functional experiments directly linking IGFBP6 to disc degeneration were provided, and the experimental data remain limited. Despite these gaps, the observed robust genetic segregation underlines the potential of this variant to serve as a biomarker in clinical settings. Key take‑home: While further replication and functional validation are warranted, the IGFBP6 c.430T>C (p.Ser144Pro) variant shows clinical utility for familial disc degeneration workup.

References

• Genetic testing and molecular biomarkers • 2017 • Whole Exome Sequencing Identified a Novel IGFBP6 Variant in a Disc Degeneration Pedigree PMID:28829625

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