Sporadic Hirschsprung Disease: Mutational Spectrum and Novel Candidate Genes Revealed by Next-generation Sequencing.

ABSTRACT: Hirschsprung disease (HSCR) is a common cause of functional colonic obstruction in children. The currently available genetic testing is often inadequate as it mainly focuses on RET and several other genes, accounting for only 15-20% of cases. To identify novel, potentially pathogenic variants, we isolated a panel of genes from a whole-exome sequencing study and from the published mouse aganglionosis phenotypes, enteric nervous system development, and a literature review. The coding exons of 172 genes were analyzed in 83 sporadic patients using next-generation sequencing. Rare stop-gain, splice-site variants, frameshift and in-frame insertions/deletions and non-synonymous variants (conserved and predicted to be deleterious) were prioritized as the most promising variants to have an effect o

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC5666020 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature