Profile Pemenang Young Scientist

  • Nama : dr. Gunadi, Ph.D
  • TTL : Banyuwangi, 19 November 1979
  • Jabatan : Lektor
  • Institusi : Fakultas Kedokteran Universitas Gadjah Mada/RSUP Dr. Sardjito
  • Alamat : Jl. Kesehatan No. 1 Sleman Yogyakarta 55281
  • Email :





Nama & Tempat
Perguruan Tinggi

Tahun Lulus



Molecular Genetics

Johns Hopkins University School of Medicine, Baltimore, MD, USA




Molecular Genetics

Kobe University Graduate School of Medicine, Kobe, Japan





UGM, Yogyakarta



Pengalaman Profesional




Bidang Pekerjaan




Editorial Board


Journal of the Medical Sciences



Research Fellow (DIKTI-FULBRIGHT Senior Research Program)


Johns Hopkins University School of Medicine, USA



PPDS Ilmu Bedah Anak

Pelayanan pasien Bedah Anak

Prodi Ilmu Bedah Anak, FK UGM/ RSUP Dr. Sardjito



Staf Pengajar, Peneliti

Pendidikan, Penelitian

Bagian Ilmu Bedah, FK UGM/ RSUP Dr. Sardjito



Research Assistant


RIKEN Center for Developmental Biology, Japan



Graduate Student (Ph.D) – Laboratory Assistant


Kobe University Graduate School of Medicine, Japan



Dokter Umum

Pelayanan pasien Umum

Klinik 24 jam, Karawang, Jabar


Ringkasan Penelitian Young Scientist

1. Comprehensive analysis of RET and NRG1 polymorphisms as risk factors for Hirschsprung disease in Indonesian population

Journal of Pediatric Surgery (2014 – in press)

Gunadi1,3, Ashish Kapoor3, Albee Yun Ling3, Rochadi1, Akhmad Makhmudi1, Elisabeth Siti Herini2, Maria X. Sosa3, Sumantra Chatterjee3, Aravinda Chakravarti3

1Pediatric Surgery Division, Department of Surgery and 2Department of Child Health Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia; 3Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: Hirschsprung disease (HSCR) is the common cause of neonatal intestinal obstruction throughout the world with the highest incidence in Asian population. Although HSCR is surgically correctable, serious and even lethal complications such as Hirschsprung’s-associated enterocolitis (HAEC) can still occur, especially in patients whose diagnosis of HSCR is delayed. Therefore, early diagnosis is important to prevent complications. Three polymorphisms, rs2435357, within a conserved transcriptional enhancer of RET, and, rs7835688 and rs16879552, within intron 1 of NRG1, have been shown to be associated with HSCR.  We wished to investigate the association between these common variants and Indonesian HSCR patients.
Methods: We ascertained 60 HSCR patients of whom 45 and 15 were males and females, respectively. Among these, the degree of aganglionosis was 52 short-segment, 1 long-segment and 7 were of unknown length. All patients were sporadic non-syndromic HSCR. We had parental information and samples on 33 cases (29 parent-child trios and 4 single parent-child duos); none of the 62 parents were affected. For controls, we used 124 ethnicity-matched individuals with no diagnosis of HSCR. The three genetic markers were examined using TaqMan Genotyping Assays in genomic DNA for association studies.
Results: RET rs2435357 showed the strongest association with HSCR both by case-control analysis (p = 2.5x10-8) and transmission disequilibrium test (p = 4.2x10-6). NRG1 rs7835688 was modestly associated with HSCR only by case-control analysis (p = 4.3x10-3), whereas rs16879552 demonstrated no association (p > 0.097).  Two locus analyses of variants showed significant interactions with increased and decreased disease risks of HSCR at NRG1 but conditional on rs2435357 genotype. All genotype combinations increased risk only when rs2435357 had TT genotype and decreased risk only when rs2435357 had CT genotype. The magnitude of the increased and decreased relative risk is >3-fold for RET and NRG1 variants.
Conclusions: RET and NRG1 variants are common susceptibility factors for HSCR in Indonesia. These common variants demonstrate that development of HSCR requires joint effects of RET and NRG1 early in gut development.

2. Molecular analysis of SCN1A in Indonesian GEFS+ patients

a.  Epilepsy Research (2010;90:132—139)
b.  Pediatrics International (2010;52:234–239)

Elisabeth Siti Herinia,b, Gunadia, Indra Sari Kusuma Harahapa,c, Surini Yusoffa,d,f, Satoru Morikawaa, Suryono Yudha Patriab, Noriyuki Nishimuraa, Sunartinib, Sutaryob, Satoshi Takadae, Masafumi Matsuof, Marjan J.A. van Kempeng, Dick Lindhoutg, Hisahide Nishioa,f

Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Japan; bDepartment of Pediatrics and cDepartment of Neurology, Gadjah Mada University, Indonesia; dDepartment of Pediatrics, University Sains Malaysia; eFaculty of Health Science, Department of Nursing, Kobe University School of Medicine, Japan; fDepartment of Pediatrics, Kobe University Graduate School of Medicine, Japan; gDepartment of Medical Genetics, University Medical Center Utrecht, Netherlands

Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) is a childhood genetic epilepsy syndrome. GEFS+ includes a wide spectrum of clinical manifestations, and SCN1A mutations have frequently been reported among the GEFS+-related gene abnormalities. In this study, we wished to clarify the distributions of the clinical subtypes of GEFS+ and the contributions of SCN1A mutations to the development of the GEFS+ subtypes.

Methods: We analyzed 34 families with GEFS+ in Indonesia using the hospital records of the patients and questionnaires for the family members. SCN1A was screened for mutations using a combination of polymerase chain reaction and denaturing high performance liquid chromatography. Nucleotide substitutions were confirmed on direct sequencing. 

Results: The number of patients with febrile seizures plus (FS+), FS+ and afebrile generalized/partial seizures, borderline severe myoclonic epilepsy in infancy (SMEB) and severe myoclonic epilepsy in infancy (SMEI) were 9, 11, 7, and 7, respectively. Most patients had a family history of febrile seizures. Only 3 of 34 probands showed SCN1A mutations. These mutations were two novel missense mutations, p.V1612I and p.C1756G, in two patients with SMEI and SMEB, and one silent mutation, p.G1762G, in a patient with FS+ and afebrile partial seizures. Both amino acid substitutions might disrupt these highly conserved regions in species from drosophila to human, leading to dysfunction of the protein. p.V1612I and p.C1756G were determined as disease-causing mutations due to their absence in the control population 

Conclusions: Two novel SCN1A mutations are identified in Indonesian population, p.V1612I and p.C1756G, which may lead to neuronal excitability or convulsions. The majority of GEFS+ patients in Indonesia were not associated with SCN1A mutations. To detect the GEFS+-causing mutations, we must search and analyze other genes in these patients.

3. Mutation analysis of ED1 gene in X-linked hypohidrotic ectodermal (XLHED) dysplasia patients Pediatric Research (2009;65:453-457)

Gunadi, Kenji Miura, Chikako Nishigori, Masafumi Matsuo, Hisahide Nishio

Department of Genetic Epidemiology, Laboratory for Applied Genome Science and Bioinformatics, Department of Dermatology and Department of Pediatrics, Kobe University Graduate School of Medicine, Japan

Purpose: X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by hypodontia, hypotrichosis, and hypohidrosis, is caused by mutations in ED1, the gene encoding ectodysplasin-A (EDA). This protein belongs to the tumor necrosis factor ligand superfamily. Many mutations in ED1 in various countries have been reported. Affected males showed most or all of the typical phenotypes of XLHED. However, only a few studies have reported the relationship between nucleotide substitution and protein structure 

Methods: Two Japanese patients with XLHED were enrolled in this study. Informed consent was obtained from the parents before DNA sampling. This study was approved by the Kobe University ethical committee. One hundred healthy Japanese adults volunteered to participate in the study as control subjects. To screen for a mutation in ED1, DHPLC analysis was performed. To identify and confirm the mutation, direct sequencing analysis was performed with a BigDye Terminator V3.0 Cycle Sequencing Kit and a genetic analyzer with DNA Sequencing Analysis Software. 

Results: In patient 1, we identified a 4-nucleotide insertion, c.119-120insTGTG, in exon 1, which led to a frameshift mutation starting from that point (p.L40fsX100). The patient’s mother was heterozygous for this mutation. In patient 2, we identified a novel missense mutation, c.1141G>C, in exon 9, which led to a substitution of glycine with arginine in the TNFL domain of EDA (p.G381R). This patient’s mother and siblings showed neither symptoms nor ED1 mutations, so this mutation was believed to be a de novo mutation in maternal germline cells. According to molecular simulation analysis of protein structure and electrostatic surface, p.G381R increases the distance between K375 in monomer A and K327 in monomer B, which suggests an alteration of overall structure of EDA. 

Conclusions: We identified two novel mutations, p.L40fsX100 and p.G381R, in ED1 of two XLHED patients. Simulation analysis suggested that the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall EDA structure.

Penghargaan yang pernah Didapatkan

  1. Travel grant – the 51st Annual Meeting of Japanese Society of Pediatric Surgeons, Osaka, May 8-10, 2014
  2. Best oral abstract, 3rd prize – the 8th ASEAN Congress of Pediatric Surgeon, Singapore, November 8-9, 2013
  3. Incentive for International Publication, Faculty of Medicine, UGM, December 19, 2013
  4. DIKTI – FULBRIGHT Senior Research Program Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, April 1 – July 31, 2013
  5. Incentive for International Publication, PHKI-C, UGM, 2010
  6. Young Investigator Award, the 50th Meeting of the Japanese Society of Child Neurology, Tokyo, May 30, 2008
  7. Monbukagakusho Scholarship for Ph.D Program, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan, October 1, 2005 – March 31, 2009
  8. Academic Excellent Award, Medical Doctor Graduation Ceremony, UGM, Yogyakarta, Indonesia, October 30, 2004
  9. Best Student, Bachelor Graduation Ceremony of UGM, Yogyakarta, Indonesia, August 19, 2002

Publikasi yang pernah Diterbitkan

  1. Gunadi, Kapoor A, Ling AY, et al. Effects of RET and NRG1 polymorphisms in Indonesian patients with Hirschsprung disease. J Pediatr Surg. 2014 – in press.
  2. Kumamoto T, Toma K, Gunadi, et al. Foxg1 Coordinates the Switch from Nonradially to Radially Migrating Glutamatergic Subtypes in the Neocortex through Spatiotemporal Repression. Cell Rep. 2013;3:931-45.
  3. Marini M, Sasongko TH, Watihayati MS, et al. Allele-specific PCR for a cost-effective & time-efficient diagnostic screening of spinal muscular atrophy. Indian J Med Res. 2012;135:31-5.
  4. Harahap IS, Saito T, San LP, et al. Valproic acid increases SMN2 expression and modulates SF2/ASF and hnRNPA1 expression in SMA fibroblast cell lines. Brain Dev. 2012;34:213-22.
  5. Sasongko TH, Gunadi, Zilfalil BA, et al. Deletion analysis of SMN1 exon 7 alone may be necessary and sufficient for the diagnosis of Spinal Muscular Atrophy. J Neurogenet. 2011;25:15-6.
  6. Harahap ISK, Sasaki N, Gunadi, et al. Herbal medicine containing Licorice may be contraindicated for a patient with an HSD11B2 mutation. Evid Based Complement Alternat Med. 2011; 2011:646540.
  7. Herini ES, Gunadi, Harahap IS, et al. Generalized Epilepsy with Febrile Seizures plus (GEFS+) spectrum: Clinical manifestations and SCN1A mutations in Indonesian patients. Epilepsy Res. 2010;90:132-9.
  8. Yusoff S, Takeuchi A, Ashi C, et al. A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for Neonatal Jaundice in the Malay population. Pediatr Res. 2010;67:401-6.
  9. Herini ES, Gunadi, van Kempen MJ, et al. Novel SCN1A mutations in Indonesian patients with Severe Myoclonic Epilepsy in Infancy. Pediatr Int. 2010;52:234–9.
  10. Sasongko TH, Gunadi, Yusoff S, et al. Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder. Brain Dev. 2010;32:385-9.
  11. Gunadi, Miura K, Ohta M, et al. Two novel mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia. Pediatr Res. 2009;65:453-7.
  12. Irimura S, Kitamura K, Kato N, et al. HnRNP C1/C2 may regulate exon 7 splicing in the Spinal Muscular Atrophy gene SMN1. Kobe J Med Sci. 2009;54:E227-36.
  13. Gunadi, Sasongko TH, Yusoff S, et al. Hypomutability at the polyadenine tract in SMN intron 3 shows the invariability of the a-SMN protein structure. Ann Hum Genet. 2008;72:288-91.
  14. Tran VK, Sasongko TH, Hong DD, et al. SMN2 and NAIP gene dosages in Vietnamese patients with spinal muscular atrophy. Pediatr Int. 2008;50:346-51.
  15. Sadewa AH, Sasongko TH, Gunadi, et al. A germ-line mutation of KCNQ2, p.R213W, in a Japanese family with BFNC. Pediatr Int. 2008;50:167-71.
  16. Syampurnawati M, Tatsumi E, Ardianto B, et al. DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation. Leuk Res. 2008;32:1141-3.
  17. Sasongko TH, Wataya-Kaneda M, Koterazawa K, et al. Novel mutations in 21 patients with Tuberous Sclerosis Complex and variation of tandem splice-acceptor sites in TSC1 exon 14. Kobe J Med Sci. 2008;54:E73-81.
  18. Kotani T, Sutomo R, Sasongko TH, et al. A novel mutation at the N-terminal of SMN Tudor domain inhibits its interaction with target proteins. J Neurol. 2007;254:624-30.
  19. Sasongko TH, Sadewa AH, Gunadi, et al. Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndrome. Kobe J Med Sci. 2007;53:157-62.