Identification of novel responsible genes for familial adenomatous polyposis

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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.