The reported CDH1 constitutional alterations are defined as truncating, deletion, insertion, splice site, non-sense, and missense mutations (Table 1); we grouped these mutations as non-missense (truncating, deletion, insertion, splice site and non sense) or missense mutations.
A segmental chromosomal alteration was defined as either the presence of an aberration of the respective chromosome arm, as determined by FISH, or in the case of deletion or imbalance, as determined by LOH.
We have also annotated variants as "reported pathogenic" or "benign" when a gene alteration was defined as such in a published article or as a "variant of unknown clinical significance" otherwise.
A copy number alteration was defined as exceeding the significance threshold of 1 × 10−6 in a minimum of 5 consecutive probes and in more than 30% of the samples.
Cognitive change being defined as an alteration of one or more standard deviation in two or more cognitive domains, the analysis as to how many patients changed with regard to their cognitive function classified 8 patients as having significantly profited from intervention.
The alteration procedure is defined as, begin{aligned} G_{s x,y)}= {left{ begin{array}{ll} {G_{d x,y)}+1},& mathrm{{if}}quad G_{d x,y)}>PP G_{d x,y }, & mathrm{{otherwise}}. end{array}right.
Copy-number alterations (CNAs) were defined as gains and losses when base 2 logarithm of the T/R ratios were >0.3219 and <−0.3219, respectively.
Potentially functional mutations were defined as nonsynonymous coding sequence alterations, or any sequence alterations within 10 bases of an intron/exon boundary.
