AB071. Semaphorin 3D impact in Indonesian Hirschsprung patients

Background: Hirschsprung disease (HSCR) is a heterogeneous genetic disorder characterized by absence of ganglion cells along the intestines, results in functional bowel obstruction in children. Recently, Semaphorin 3D (SEMA3D) gene has been implicated in the pathogenesis of intestinal ganglionosis. We aimed to conduct a mutation analysis of SEMA3D gene in HSCR patients in Indonesia, a genetically distinct group within Asia.

Methods: We ascertained 40 patients with HSCR of whom 27 and 13 were males and females, respectively. Subsequently, we performed direct sequencing to clarify the contribution of SEMA3D gene to HSCR development.

Results: All patients were sporadic HSCR with degree of aganglionosis as follows: short-segment in 39/40 (98%) patients and long-segment in 1/40 (2%) patients. Transanal endorectal pull-through (TEPT) has been the most common definitive surgery (54%), followed by Duhamel (21%), and Soave (14%). Mutation analysis of SEMA3D gene showed no rare variant, but one common variant in exon 17, rs7800072. The risk allele frequency at rs7800072 (C) among HSCR patients were 0.52.

Conclusions: This result implies that the SEMA3D gene may not have an effect in the molecular pathogenesis of HSCR, particularly in Indonesia. This study is the first report of SEMA3D gene in Asian ancestry. Further study with multicenter and a larger number of samples is necessary to clarify the results.

Keywords: Hirschsprung disease (HSCR); Semaphorin 3D (SEMA3D); Indonesia; Asian ancestry