title: Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients.
abstract: Mutation and polymorphism data for Hirschsprung disease (HSCR) varies among ethnic groups. Single nucleotide polymorphisms (SNP) of RET proto-oncogene (RET) were recently shown to be associated with the disease, and with disease severity, in different populations. In this study, comprehensive analysis of RET, GDNF, EDNRB, ET-3, and SOX-10 genes among sporadic HSCR in Thailand was conducted by standard PCR-SSCP, RFLP, and sequencing methods. Of 41 patients, 30 cases had rectosigmoid disease (RSD) and 11 cases were assigned to the long-segment disease (LSD) group. Four missense mutations of RET, S100M, R231H, T278N, and G533S, were identified in three patients. One novel missense mutation, V111Q, was detected in EDNRB. For ET-3, two novel missense mutations, D166E and C173R, occurred concomitantly in a patient. The incidence of missense mutation was significantly higher in our female HSCR patient than in the male counterpart. Statistical analysis of the SNPs revealed a significant difference between allele distribution of RET L769L in patients in the LSD and RSD groups. The predominant genotype construct of RET A45A/L769L in our HSCR was GG/GG, which is obviously different from results from all previous studies. The GG/GG genotype construct was associated with RSD and with males. The study also detected a variant allele of RET S836S which has never been reported in Asian cohorts.
authors.affiliation: Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hadyai, Songkhla, 90110, Thailand. surasak.sa@psu.ac.th.|Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. surasak.sa@psu.ac.th.
authors.forename: Surasak
authors.initials: S
authors.lastname: Sangkhathat
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kusafuka
authors.affiliation: Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hadyai, Songkhla, 90110, Thailand.
authors.forename: Piyawan
authors.initials: P
authors.lastname: Chengkriwate
authors.affiliation: Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hadyai, Songkhla, 90110, Thailand.
authors.forename: Sakda
authors.initials: S
authors.lastname: Patrapinyokul
authors.affiliation: Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hadyai, Songkhla, 90110, Thailand.
authors.forename: Burapat
authors.initials: B
authors.lastname: Sangthong
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
mesh_terms: D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics; D055757:SOXE Transcription Factors; D013785:Thailand; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006609:High Mobility Group Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D044023:Receptor, Endothelin B; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human