Colorectal adenomatous polyposis associated with MYH mutations:: Genotype and phenotype characteristics

PURPOSE:Recent literature reports that several digestive diseases are associated with mutations in the base excision repair gene MYH. This study was designed to establish the prevalence of germ-line MYH mutations in a series of 56 consecutive patients with no detectable APC mutation and describe the phenotype of those with MYH mutations. METHODS:MYH mutations were screened by DNA sequencing after polymerase chain reaction amplification of each exon. Clinical, endoscopic, and surgical data were collected for the tested patients. RESULTS:MYH mutations were identified only in the group of patients with attenuated adenomatous polyposis with ten or more adenomatous polyps. The prevalence of MYH mutations was 34.4 percent (11 cases) in this subgroup of 30 patients. There were two homozygotes and eight compound heterozygotes. Only one patient had a monoallelic mutation. At least one of two mutational hot spots was identified in ten patients. Three patients presented with a family history of adenomatous polyposis in siblings, without vertical transmission. The median number of colorectal adenomatous polyps was 53 without preferential localization. Colorectal cancer was associated with polyposis in seven patients. Gastric and duodenal adenomas were diagnosed in one case. Ten of 11 patients underwent colectomy. CONCLUSIONS:MYH mutations have been observed in one-third of patients with attenuated polyposis. The phenotype of the disease is similar to attenuated familial adenomatous polyposis. Upper gastrointestinal endoscopy also should be recommended. However, its transmission shows evidence of a recessive pattern.