Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development.

ABSTRACT: Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups

SUBMITTER: Kuil LE 

PROVIDER: S-EPMC8372947 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature