@entity1963 ( @entity1963 ; OMIM 142623) is a @entity245 characterized by @entity1963 along variable lengths of the distal gastrointestinal tract, which results in @entity1321 . Interactions among known @entity1963 genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this @entity74 . We have performed whole exome sequencing of 16 @entity1963 @entity1 from 8 unrelated families with @entity5 platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the @entity68493 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for @entity45694 and several genes (N   =   23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving @entity68493 , @entity1963 known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial @entity1963 .

Exome sequencing reveals a high genetic heterogeneity on XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity68493 :: ('120114', 'Gene') :: ['FAT3'] @entity5 :: ('MESH:D009369', 'Disease') :: ['SOLID'] @entity1963 :: ('MESH:D006627', 'Disease') :: ['HSCR', 'aganglionosis', 'Hirschsprung disease'] @entity245 :: ('MESH:D002658', 'Disease') :: ['developmental disorder'] @entity74 :: ('MESH:D030342', 'Disease') :: ['complex genetic disorder'] @entity1321 :: ('MESH:D007415', 'Disease') :: ['intestinal obstruction'] @entity45694 :: ('79026', 'Gene') :: ['AHNAK']
@entity74 :: (MESH:D030342,Disease) :: ['familial Hirschsprung disease']
