Hirschsprung disease (HSCR)
Our research focus on understanding of susceptibility genes for Hirschsprung disease (HSCR), its complications (such as enterocolitis and persistent bowel symsptoms), treatment and HSCR patient’s outcomes following surgery for which we were recently awarded a multiyear Indonesian Ministry of Higher Education, Research and Technology/Ministry of Research and Technology – National Agency for Research and Innovation. Our goal is how this genetic information can be used for disease prediction and management for better patient services and their quality of life (translational research).
HSCR is the most common cause of functional obstruction in neonates due to disruption in the development of enteric nervous system (ENS), characterised by the lack of ganglion cells in the intestines due to disorder in the neural crest cell migration, proliferation, and differentiation process. Its incidence in Indonesia is higher (1:3,250) than other population, including Asia (1:3,600) and Caucasian (1:6,700). It might be associated with the differences in the allele frequency RET rs2435357 and rs2506030. There are at least 17 genes (and miRNAs) involved in the pathogenesis of HSCR, including RET, EDNRB, GRFa1, GDNF, SOX10, NRG1, SEMA3C, SEMA3D, etc. We have investigated the role of genetic variants and expressions of several genes and miRNA in our cohort patients, including RET, NRG1, SEMA3C, SEMA3C, NRG1, SEMA3D, SK3, UBR4 and miRNA-206. We have now further analysed the exomes and transcriptomes using the high-throughput next-generation sequencing.
Biliary Atresia (BA)
Biliary atresia (BA) is characterized by a fibro-obliterative disorder of the intra- and extrahepatic biliary system in infants, resulting in end-stage liver disease if the Roux-en-Y portoenterostomy (Kasai) surgery is not conducted at earlier age. Its incidence varies among population, from 1:5–7000 in Asian to 1:15–20,000 in Caucasian.
Although some biomarkers of hepatic progenitor cells have been reported to be involved in the liver fibrosis of BA patients, the findings are still controversial. We have investigated the expressions of several genes and non-coding RNA involved in the pathogenesis of liver fibrosis in our cohort patients, including miRNA-21, PTEN lncRNA APTR, Fn14 and CD133.
References:
Gunadi, Kapoor A, Ling AY, et al. J Pediatr Surg. 2014;49:1614-8.
Gunadi, Makhmudi A, Agustriani N, Rochadi. Pediatr Surg Int. 2016;32:1025-8.
Gunadi, Budi NYP, Sethi R, et al. BMC Pediatr. 2018;18:292.
Gunadi, Sunardi M, Budi NYP, et al. BMC Med Genet. 2018;19:24.
Gunadi, Iskandar K, Makhmudi A, Kapoor A. J Surg Res. 2019;233:96-9.
Gunadi, Budi NYP, Kalim AS et al. Orphanet J Rare Dis. 2019;14:5
Gunadi, Kalim AS, Liana E, et al. BMC Pediatr. 2019;19:493.
Gunadi, Kalim AS, Budi NYP, et al. Front Pediatr. 2020;8:60
Makhmudi A, Kalim AS, Gunadi. BMC Res Notes. 2019;12:189.
Makhmudi A, Supanji R, Putra BP, Gunadi. Pediatr Surg Int. 2020;36:75-79
Contact us:
Genetics Working Group (Pokja Genetik)
Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
Jl. Kesehatan No. 1 Yogyakarta 55281 Indonesia
Ph./Fax: 62274631036
Email: pokjagenetikugm@gmail.com
Web: https://pokjagenetik.fk.ugm.ac.id/genetic-testing-registry/