All individuals with an intellectual disability-related PPM1D mutation had a de novo mutation in the last or penultimate exon of PPM1D.
For general information about genes and chromosomes we refer to Genetics Home Reference.
Function
PPM1D protein is best known for its role in a pathway that restores damage of DNA. We also know that it has a function in the development of the brain, since it is expressed in the (developing) brains of humans and mice.
Type of mutations and pathogenic effect
The protein PPM1D is encoded by the PPM1D-gene. Mutations in the last part of the PPM1D-gene results in a shorter protein, which leads to an altered function. Whereas we have seen that there is no effect on a protein called p53, which is another protein that play part in the DNA damage repair pathway, our results do suggest a possible effect on the stress response pathway in another way. So how the ID-related PPM1D mutations lead to intellectual disability is currently unknown.
Diagnostic testing
Since the Jansen-de Vries syndrome is not highly recognizable, most mutations in PPM1D will be found by whole exome sequencing. But also targeted analysis of the PPM1D gene by Sanger sequencing can be performed.