UNASSIGNED: In up to 30  % of @entity1 with @entity10915 , no germline mutation in the known genes @entity1412 , causing @entity1412 , @entity20701 , causing @entity20701 -associated @entity1412 , and POLE or @entity14824 , causing Polymerase-Proofreading-associated @entity1412 can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 @entity2513 from seven unrelated @entity1 with unexplained sporadic @entity1412 . For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or @entity5 suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated @entity1 . All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes ( @entity17920 , @entity64908 , @entity70094 ). In the validation cohort, further variants predicted to be pathogenic were identified in @entity17920 and @entity64908 . According to the somatic mutation spectra, the @entity652 in this @entity1 cohort follow the classical pathways of colorectal tumorigenesis. The present study identified three candidate genes which might represent rare causes for a predisposition to @entity2513 formation. Especially @entity64908 ( @entity64908 ) and @entity70094 ( @entity70094 ) warrant further exploration. To evaluate the clinical relevance of these genes, investigation of larger @entity1 cohorts and functional studies are required.

Exome sequencing identifies potential novel candidate genes in XXXX with unexplained @entity10915 .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity10915 :: ('MESH:C563924', 'Disease') :: ['colorectal adenomatous polyposis'] @entity64908 :: ('9780', 'Gene') :: ['FAM38A', 'PIEZO1'] @entity14824 :: ('5424', 'Gene') :: ['POLD1'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity20701 :: ('4595', 'Gene') :: ['MUTYH'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity70094 :: ('125150', 'Gene') :: ['SWS1', 'ZSWIM7'] @entity1412 :: ('MESH:D011125', 'Disease') :: ['familial adenomatous polyposis', 'polyposis', 'adenomatous polyposis', 'APC'] @entity17920 :: ('1824', 'Gene') :: ['DSC2'] @entity2513 :: ('MESH:C563365', 'Disease') :: ['colorectal adenomas', 'colorectal adenoma']
@entity1 :: (9606,Species) :: ['patients']
