Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome

Emma Hilton, May Tassabehji, Ming Fang Zhi, Emma N. Hilton, Julie McGaughran, Zhongming Zhao, Charles E. De Bock, Emma Howard, Michael Malass, Dian Donnai, Ashish Diwan, Forbes D C Manson, Dédée Murrell, Raymond A. Clarke

    Research output: Contribution to journalArticlepeer-review


    Klippel-Feil syndrome (KFS) is a congenital disorder of spinal segmentation distinguished by the bony fusion of anterior/cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. Here we report mutations at the GDF6 gene locus in familial and sporadic cases of KFS including the recurrent missense mutation of an extremely conserved residue c.866T>C (p.Leu289Pro) in association with mirror movements and an inversion breakpoint downstream of the gene in association with carpal, tarsal, and vertebral fusions. GDF6 is expressed at the boundaries of the developing carpals, tarsals, and vertebrae and within the adult vertebral disc. GDF6 knockout mice are best distinguished by fusion of carpals and tarsals and GDF6 knockdown in Xenopus results in a high incidence of anterior axial defects consistent with a role for GDF6 in the etiology, diversity, and variability of KFS. © 2008 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)1017-1027
    Number of pages10
    JournalHuman Mutation
    Issue number8
    Publication statusPublished - Aug 2008


    • Development
    • Etiology
    • GDF6
    • KFS
    • Klippel-Feil
    • Vertebral fusion


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