Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis

Deborah Krakow, Stephen P. Robertson, Lily M. King, Timothy Morgan, Eiman T. Sebald, Cristina Bertolotto, Sebastian Wachsmann-Hogiu, Dora Acuna, Sandor S. Shapiro, Toshiro Takafuta, Salim Aftimos, Chong Ae Kim, Helen Firth, Carlos E. Steiner, Valerie Cormier-Daire, Andrea Superti-Furga, Luisa Bonafe, John M. Graham, Arthur Grix, Carlos A. Bacino & 5 others Judith Allanson, Martin G. Bialer, Ralph S. Lachman, David L. Rimoin, Daniel H. Cohn

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

The filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton by cross-linking actin into three-dimensional networks, linking the cell membrane to the cytoskeleton and serving as scaffolds on which intracellular signaling and protein trafficking pathways are organized (reviewed in refs. 1,2). We identified mutations in the gene encoding filamin B in four human skeletal disorders. We found homozygosity or compound heterozygosity with respect to stop-codon mutations in autosomal recessive spondylocarpotarsal syndrome (SCT, OMIM 272460) and missense mutations in individuals with autosomal dominant Larsen syndrome (OMIM 150250) and the perinatal lethal atelosteogenesis I and III phenotypes (AOI, OMIM 108720; AOIII, OMIM 108721). We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse. These data indicate an unexpected role in vertebral segmentation, joint formation and endochondral ossification for this ubiquitously expressed cytoskeletal protein.

Original languageEnglish (US)
Pages (from-to)405-410
Number of pages6
JournalNature Genetics
Volume36
Issue number4
DOIs
StatePublished - Apr 2004

Fingerprint

Filamins
Genetic Databases
Joints
Mutation
Cytoskeleton
Genes
Intracellular Signaling Peptides and Proteins
Cytoskeletal Proteins
Growth Plate
Terminator Codon
Protein Transport
Missense Mutation
Chondrocytes
Osteogenesis
Actins
Cell Membrane
Phenotype
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Krakow, D., Robertson, S. P., King, L. M., Morgan, T., Sebald, E. T., Bertolotto, C., ... Cohn, D. H. (2004). Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nature Genetics, 36(4), 405-410. https://doi.org/10.1038/ng1319

Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. / Krakow, Deborah; Robertson, Stephen P.; King, Lily M.; Morgan, Timothy; Sebald, Eiman T.; Bertolotto, Cristina; Wachsmann-Hogiu, Sebastian; Acuna, Dora; Shapiro, Sandor S.; Takafuta, Toshiro; Aftimos, Salim; Kim, Chong Ae; Firth, Helen; Steiner, Carlos E.; Cormier-Daire, Valerie; Superti-Furga, Andrea; Bonafe, Luisa; Graham, John M.; Grix, Arthur; Bacino, Carlos A.; Allanson, Judith; Bialer, Martin G.; Lachman, Ralph S.; Rimoin, David L.; Cohn, Daniel H.

In: Nature Genetics, Vol. 36, No. 4, 04.2004, p. 405-410.

Research output: Contribution to journalArticle

Krakow, D, Robertson, SP, King, LM, Morgan, T, Sebald, ET, Bertolotto, C, Wachsmann-Hogiu, S, Acuna, D, Shapiro, SS, Takafuta, T, Aftimos, S, Kim, CA, Firth, H, Steiner, CE, Cormier-Daire, V, Superti-Furga, A, Bonafe, L, Graham, JM, Grix, A, Bacino, CA, Allanson, J, Bialer, MG, Lachman, RS, Rimoin, DL & Cohn, DH 2004, 'Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis', Nature Genetics, vol. 36, no. 4, pp. 405-410. https://doi.org/10.1038/ng1319
Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C et al. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nature Genetics. 2004 Apr;36(4):405-410. https://doi.org/10.1038/ng1319
Krakow, Deborah ; Robertson, Stephen P. ; King, Lily M. ; Morgan, Timothy ; Sebald, Eiman T. ; Bertolotto, Cristina ; Wachsmann-Hogiu, Sebastian ; Acuna, Dora ; Shapiro, Sandor S. ; Takafuta, Toshiro ; Aftimos, Salim ; Kim, Chong Ae ; Firth, Helen ; Steiner, Carlos E. ; Cormier-Daire, Valerie ; Superti-Furga, Andrea ; Bonafe, Luisa ; Graham, John M. ; Grix, Arthur ; Bacino, Carlos A. ; Allanson, Judith ; Bialer, Martin G. ; Lachman, Ralph S. ; Rimoin, David L. ; Cohn, Daniel H. / Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. In: Nature Genetics. 2004 ; Vol. 36, No. 4. pp. 405-410.
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