Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

J Hum Genet. 2006;51(12):1126-1132. doi: 10.1007/s10038-006-0064-7. Epub 2006 Sep 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / ethnology
  • Asian People / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Variation
  • Genotype
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • High Mobility Group Proteins / genetics
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Mutation, Missense*
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics
  • Receptor, Endothelin B / genetics
  • SOXE Transcription Factors
  • Thailand
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • High Mobility Group Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Receptor, Endothelin B
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Transcription Factors
  • Proto-Oncogene Proteins c-ret
  • RET protein, human