Submission Details

Autosomal dominant

04/03/2019

The CDON gene is located on chromosome 11 at 11q24.2 and encodes the cell adhesion associated, oncogene regulated protein. This protein, which is a member of the immunoglobulin superfamily, is highly expressed during embryonic development and functions as part of a cell surface receptor complex in the Sonic hedgehog signalling pathway. The CDON gene was first reported in relation to an autosomal dominant form of holoprosencephaly in 2011 (21802063: Bae et al. 2011). At least five missense variants and one stop gained variant have been reported. Evidence supporting this gene-disease relationship includes case level data and experimental data. Variants in the CDON gene have been reported in at least six probands from three publications (21802063: Bae et al. 2011; 26728615: Jones et al. 2016; 26529631: Bashamboo et al. 2016). This gene-disease relationship is supported by expression studies that are consistent with the disease (10974670: Mulieri et al. 2000) and in vitro experimental data demonstrating physical protein interaction with the SHH gene, which is also associated with a holoprosencephaly phenotype (21802063: Bae et al. 2011). A homozygous mouse model showed facial defects of microform holoprosencephaly along with increased neonatal mortality, and reduction of CDON mRNA in the embryos of zebrafish and chick recapitulated the optic anomalies of the disease phenotypic spectrum (12620190: Cole et al. 2003; 25001599: Cardozo et al. 2014). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

21802063 26529631 26728615 10974670 12620190 25001599