中文摘要：

目的探讨CDXI基因外显子突变在先天性肛门直肠畸形（ARM）患儿的分布情况。方法回顾性分析2003年6月至2009年3月中国医科大学附属盛京医院及河北大学附属医院收治的108例（中国医科大学附属盛京医院85例、河北大学附属医院23例）ARM患儿和120例（中国医科大学附属盛京医院60例、河北大学附属医院60例）同期行健康体检者的临床资料。采用病例对照研究方法抽取患者外周血并提取基因组DNA后，应用PCR方法扩增CDXl基因外显子，并将PCR产物进行测序分析。正态分布的计量资料以元±s表示，采用t检验，计数资料比较采用r检验。结果108例ARM息儿进行CDXl外显子测序，在编码区共发现4例ARM患儿携带4种不同的CDXl突变位点，肛门狭窄、直肠会阴瘘、直肠前庭瘘、直肠尿道瘘患儿各1例。上述突变位点位于CDXl的高度保守的同源结构域中，1例患儿位于第1外显子（C．213～214Ins GAA），2例患儿发生于CDXl第3外显子的DNA结合区（c．6G〉C、C．27G〉T），1例患儿位于第3外显子特异性DNA结合区（C．18A〉C）。在健康体检者中未发现外显子及其他位点突变。CDX1基因中e．213～214InsGAA、c．6G〉C、c．27G〉T、C．18A〉C的突变分别引发96—981nsE、K199N、R206S、Q203H等氨基酸的改变。结论ARM患儿中存在CDX1第1外显子或第3外显子的突变，CDX1可能是ARM的易感基因。

英文摘要：

Objective To explore the distribution of exon mutations of CDX1 gene in children with congenital anorectal malformation （ARM）. Methods In a case-control study conducted between June 2003 and March 2009, 108 children with congenital ARM and 120 normal children undergoing health examinations who were admitted to the Shengjing Hospital of China Medical University （85 children with congenital ARM and 60 normal children ） and the Affiliated Hospital of Hebei University （23 children with congenital ARM and 60 normal children） were assigned to the case group and the control group, respectively. PCR was performed to extend exons of the CDX1 gene and then sequence analysis was conducted after genomic DNAs were extracted from the peripheral blood. Categorical data with normal distribution were presented as x ± s and analyzed using the t test, count data were analyzed using the chi-square test. Results Exon sequencing was performed in the case group. Four children with 4 mutations of CDX1 located at coding regions were detected, including 1 with archostegnosis, 1 with rectoperineal fistula, 1 with rectovestibular fistula and 1 with rectourethral fistula. Four mutations located at the highly conserved homology domain of the CDX1 gene. The mutations of 1 child located at exon 1 of CDX1 gene （c. 213-214Ins GAA）. The mutations of 2 children located at the splicing region to exon 3 of the CDX1 gene （ c. 6G 〉 C, c. 27G 〉 T）. The mutations of 1 child located at the idiocratic splicing region to exon 3 of the CDX1 gene（ c. 18A 〉 C）. No mutation was detected in the controls. Mutations of the CDX1 gene at c. 213-214Ins GAA, c. 6G 〉 C, c. 27G 〉 T, and c. 18A 〉 C, respectively, resulted in amino acid substitutions at 96-98Ins E, K199N, R206S, and Q203H in the protein. Conclusion Exon 1 or 3 mutations of the CDX1 gene is identified in children with congenital ARM, and CDX1 gene may be a susceptibility gene for ARM.