Identification of novel responsible genes for familial adenomatous polyposis

应用聚合酶链式反应-单链构象多态性和直接测序法分析了家族性腺瘤性息肉病(FAP)患者磷脂酶(Pla2g2a)基因和MUTYH(MYH)基因的种系突变。还研究了可能的基因-表型相关性。在45个家系的59例FAP患者中，Pl2g2a基因第3外显子32位密码子的突变最为常见。在Pla2g2a基因突变阳性组中，胃底腺息肉较多见，壶腹腺瘤、胃腺瘤和骨瘤较少见。Logistic回归分析显示胃底腺息肉依赖于幽门螺杆菌感染，胃腺瘤和壶腹腺瘤依赖于Pla2g2a突变。MYH基因有5个错义突变，其中外显子12(H324Q)突变最为常见。但根据MYH基因突变对患者进行分型时，两组间无明显差异。有一例患者存在G272Q和A359V的双等位突变。另有1例P18L和G25S复合异基因突变。这两名患者均未发现APC基因突变。这些结果提示，Pla2g2a基因是FAP的修饰基因之一，MYH基因的双等位突变是FAP无APC基因突变的原因。

We analyzed germline mutations of phospholipase (Pla2g2a) gene and MUTYH (MYH) gene in patients with familial adenomatous polyposis(FAP) by means of PCR-SSCP and direct sequence. Possible genotype-phenotype correlation was also investigated. Among 59 patients from 45 families with FAP, codon 32 in exon 3 of Pla2g2a gene was the most frequently mutated. Fundic gland polyposis was more frequent, and ampullary adenoma, gastic adenoma and osteoma were less frequent in patients with positive Pla2g2a mutation than those without. A logistic regression analysis revealed fundic gland polyposis to be dependent on Helicobacter pylori infection and gastric and ampullary adenomas to be dependent on Pla2g2a mutation. There were five missence mutations in MYH gene, among which a mutation in exon 12(H324Q) was the most frequent. However, there were no differences in genotype when patients were divided accodring to the mutation of MYH gene. There was a patient with bialleic mutations with G272Q and A359V. There was another patient with compound heterogenic mutations in P18L and G25S. These two patients were free from APC gene mutations. These findings suggest that Pla2g2a gene is one of modifier genes in FAP, and that bialleic mutation of MYH gene is responsible for FAP without APC gene mutation.