Molecular characteristics
CTNNB1 is located on chromosome 3p22.1 with a of 23.3kb and consists of 16 exons. It encodes for β-Catenin, which is not only a coactivator in the Wnt-signalling pathway but also a key component in cadherin adhesion complex essential in cell-cell adhesion.
Type of mutations
The majority of the reported disease-causing variants are loss-of-function leading to haploinsufficiency, but missense variants have also been reported. No definite genotype-phenotype correlation has been delineated, but it was proposed that haploinsufficiency is associated with FEVR, while variants escaping nonsense mediated mRNA decay or altering the uncharacterized carboxy-terminal domain of β-Catenin are associated with a milder phenotype of non-syndomic FEVR.
Most of the reported variants are de novo. Inherited variants have been identified also. Germline mosaicism has been reported in at least one family.
Diagnostic testing
CTNNB1 disease-causing variants can be identified by exome/genome sequencing. Some of the individuals had microdeletions involving the CTNNB1 gene identified through microarray.
CTNNB1