Mutations in two regions of FLNB result in atelosteogenesis I and III

Claire Farrington-Rock, Marc H Firestein, Louise S Bicknell, Andrea Superti-Furga, Carlos A Bacino, Valerie Cormier-Daire, Martine Le Merrer, Clarisse Baumann, Joelle Roume, Patrick Rump, Joke B G M Verheij, Elizabeth Sweeney, David L Rimoin, Ralph S Lachman, Stephen P Robertson, Daniel H Cohn, Deborah Krakow

Research output: Contribution to journalArticlepeer-review


The filamins are a family of cytoplasmic proteins that bind to and organize actin filaments, link membrane proteins to the cytoskeleton, and provide a scaffold for signaling molecules. Mutations in the gene encoding filamin B (FLNB) cause a spectrum of osteochondrodysplasias, including atelosteogenesis type I (AOI) and atelosteogenesis type III (AOIII). AOI and AOIII are autosomal dominant lethal skeletal dysplasias characterized by overlapping clinical findings that include vertebral abnormalities, disharmonious skeletal maturation, hypoplastic long bones, and joint dislocations. Previous studies have shown that heterozygosity for missense mutations that alter the CH2 domain and repeat 6 region of filamin B produce AOI and AOIII. In this study, 14 novel missense mutations in FLNB were found in 15 unrelated patients with AOI and AOIII. The majority of the mutations resided in exon 2 and exon 3, which encode the CH2 domain of the actin-binding region of filamin B. The remaining mutations were found in exon 28 and exon 29, which encode repeats 14 and 15 of filamin B. These results show that clustering of mutations in two regions of FLNB produce AOI/AOIII, and highlight the important role of this cytoskeletal protein in normal skeletogenesis.
Original languageEnglish
Pages (from-to)705-10
Number of pages6
JournalHuman Mutation
Issue number7
Publication statusPublished - 2006


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