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The molecular basis of oral-facial-digital syndrome, type 1


  • Marina Macca,

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    • Marina Macca, MD, trained at the Department of Pediatrics of the Federico II University of Naples and now works at the Department of Phisical and Rehabilitation Medicine at the same University. Her clinical and research interest is child disability with a special focus on neurogenetic disorders.

  • Brunella Franco

    Corresponding author
    • Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
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    • Brunella Franco, MD. is a Human Geneticist at the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, Italy. She also holds an appointment as Associate Professor of Medical Genetics at the Federico II University in Naples, Italy. She published over 80 publications in the field of Human Genetics. Her principal interest is the understanding of the mechanisms underlying human genetic disorders.

  • How to cite this article: Macca M, Franco B. 2009. The molecular basis of oral–facial–digital syndrome, type 1. Am J Med Genet Part C Semin Med Genet 151C:318–325.


Oral–facial–digital syndrome type 1 (OFDI; OFD1; OMIM 311200) is a rare developmental disorder transmitted as an X-linked dominant condition with embryonic male lethality. OFD1 is characterized by malformation of the oral cavity, face, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This disorder is due to mutations in the OFD1 gene that encodes a centrosomal protein localized at the basal bodies at the origin of primary cilia. Characterization of in vitro and in vivo models demonstrated that, similarly to what described for other ciliary proteins, Ofd1 inactivation is associated to defective sonic hedgehog (Shh) and canonical Wnt signaling pathways. Functional studies have demonstrated that OFD1 has a crucial role in the biology of primary cilia thus ascribing this pleiotropic disease to the growing number of disorders associated to dysfunction of primary cilia. OFD1 shares phenotypic similarities with this latter group of disorders, such as cystic kidneys, skeletal, and CNS abnormalities. Future studies will address whether all clinical manifestations of these diseases can be entirely explained by cilia dysfunction or may also be due to direct roles of the proteins involved. © 2009 Wiley-Liss, Inc.