Sangkhathat Surasak, Kusafuka Takeshi, Chengkriwate Piyawan, Patrapinyokul Sakda, Sangthong Burapat, Fukuzawa Masahiro
Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hadyai, Songkhla, 90110, Thailand.
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Hum Genet. 2006;51(12):1126-1132. doi: 10.1007/s10038-006-0064-7. Epub 2006 Sep 29.
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.
先天性巨结肠症（HSCR）的突变和多态性数据在不同种族群体中存在差异。RET原癌基因（RET）的单核苷酸多态性（SNP）最近显示在不同人群中与该疾病及其严重程度相关。在本研究中，采用标准PCR-SSCP、RFLP和测序方法，对泰国散发性HSCR患者的RET、GDNF、EDNRB、ET-3和SOX-10基因进行了综合分析。41例患者中，30例为直肠乙状结肠疾病（RSD），11例被归入长段疾病（LSD）组。在3例患者中鉴定出RET的4个错义突变，即S100M、R231H、T278N和G533S。在EDNRB中检测到1个新的错义突变V111Q。对于ET-3，1例患者同时出现2个新的错义突变D166E和C173R。我们的女性HSCR患者错义突变的发生率显著高于男性患者。对SNP的统计分析显示，LSD组和RSD组患者RET L769L的等位基因分布存在显著差异。我们的HSCR患者中RET A45A/L769L的主要基因型结构为GG/GG，这与以往所有研究结果明显不同。GG/GG基因型结构与RSD和男性相关。该研究还检测到RET S836S的一个变异等位基因，这在亚洲队列中从未报道过。
