Pathogenic variants of ANKRD11 have been reported to cause KBG syndrome characterized by short stature, characteristic facial appearance, intellectual disability, macrodontia, and skeletal anomalies.
Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.
ANKRD11 thus serves as a candidate tumor suppressor gene and it has been speculated that its haploinsufficiency may lead to an increased cancer risk in KBG syndrome patients.
On the other hand, patients carrying either deletions encompassing solely ANKRD11 or its loss-of-function variants were reported in association with the KBG syndrome, characterized by a very similar phenotype, including mild-to-moderate intellectual disability, short stature and macrodontia of upper incisors, with inter and intrafamilial variability.
This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in <i>ANKRD11,</i> thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome.
This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in <i>ANKRD11,</i> thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome.
We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.
We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.