Significant Association of rs2147555 Genetic Polymorphism in the EDNRB Gene with Hirschsprung Disease in Southern Chinese Children

Hirschsprung disease (HSCR) is a human birth defect at the clinical setting, usually characterized by an absent enteric nervous system (ENS) from the distal bowel. The majority of HSCR cases represent a complex disorder resulting from the interaction of multiple genetic and environmental factors. Genetic events have been described to be involved in the abnormal development of the enteric nervous system. Although variants in several genes like RET and EDNRB have been suggested to contribute major risks to HSCR, very little is known about their involvement in the onset of HSCR. Here, we studied a large Chinese Han cohort consisting of 1,470 HSCR patients and 1,473 non-HSCR controls to further test whether there are more variants in EDNRB associated with HSCR. Our results provided the first evidence that rs2147555 in EDNRB confers a significant risk of HSCR in a Chinese Han population for both allelic frequencies ( P = 4.16 × 10 − 3 ; OR = 1.29 ) and genotypic frequencies assuming either a dominant or recessive model ( P = 0.011 and P = 0.027 , respectively). When different subtypes of HSCR cases were analyzed, the association remained significant ( OR = 1.33 , P = 0.003 for short-segment HSCR; OR = 1.34 , P = 0.044 for long segment HSCR).

A Rare Co-occurrence of Intestinal Malrotation and Hirschsprung's Disease in a Neonate with 13q21.31q33.1 Interstitial Deletion Including the EDNRB Gene

We report a rare co-occurrence of intestinal malrotation and Hirschsprung's disease (HSCR) in a male neonate with a large 38.8 Mb interstitial deletion of chromosome 13 extending from q21.31 to q33.1 including the EDNRB gene, who presented with craniofacial dysmorphic features and central nervous system malformations. The loss of EDNRB gene in addition to bilateral hearing loss and HSCR suggested an additional diagnosis of Waardenburg–Shah's syndrome. This case highlights the fact that prior knowledge of this rare association in infants with 13q deletion syndrome would enable early diagnosis and prompt interventions to prevent gastrointestinal complications.