Case Report of a New Mutation in MYH-Associated Polyposis

MYH-associated polyposis is an autosomal recessive disorder recognized in the last 10 years. Here we describe a case with a never reported mutation in MYH gene resulting in MYH-associated polyposis. Porpiglia SA, Hall JM, Meyer EJ, Forman DA, Rybak C, Fleider FD, Cooper SH and Farma MJ* Fox Chase Cancer Center, Philadelphia, USA Farma MJ, et al. Clinics in Surgery Colon and Rectal Surgery Remedy Publications LLC., | http://clinicsinsurgery.com/ 2016 | Volume 1 | Article 1063 2 identified [13]. The deletion of exon 7 in the MYH gene has not previously been described. MYH mutations account for 0.4-1% of colorectal cancers [14,15]. In addition, in the literature 58-60% of patients with polyposis will have colorectal carcinoma [5,16]. Individuals with MYH associated polyposis (MAP) have between 10 and >100 polyps on age of presentation. There have been series looking at the association of phenotype and genotype. Nielson, et al published a large series of 257 patients with MAP reviewing the phenotypes and genotypes of these patients and found Y179C had more severe phenotype. One reason for this more severe phenotype is patients with mutations in G396D typically present at a mean age of 51 years compared to patients with Y179C mutations who present at a mean age of 43 years [5]. Furthermore, 15% of those with G396D mutations had more than 100 polyps and 20% had fewer than 10 polyps compared to Y179C homozygotes where 29% had more than 100 polyps and only 2% had fewer than 10 polyps [5]. Patients with MUTYH mutations are phenotypically similar to attenuated FAP (a milder form of FAP) [17]. However, patients tend to have hyperplastic and sessile serrated polyps [18]. Current screening guidelines from the National Comprehensive Cancer Network (NCCN) recommend testing for MUTYH if there is a personal history of greater than 10 adenomas, the person has known family members with biallelic MUTYH mutations, or those who meet criteria for serrated polyposis syndrome. In addition, when a person presents with polyposis APC mutations should be tested for first and then testing for the two most common northern European founder MUTYH mutations [19]. The current guidelines do not recommend screening the entire MUTYH gene, but only if one founder mutation is identified. Our patient had a homozygous deletion of exon 7 and would not have been identified by routine screening. In addition, the patient is a Coptic Christian from Egypt, a group of people with limited sequence data. The mutational analysis was performed by Myriad Genetic Laboratories. They recently reviewed their patients that had undergone genetic testing for MUTYH founder mutations and patients with colorectal cancer younger than age 50 and less than 10 adenomas. The patients screened for MUTYH founder mutations, 25% had additional MUTYH mutations identified. In addition, those screened who were younger than 50 or less than 10 adenomas, 20% had biallelic mutations that otherwise would have been categorized to monoallelic [20]. Therefore, mutations in MUTYH may be missed in patients being tested only for founder mutations. Conclusion Our patient has a mutation not previously described in the MYH gene and the mutation is not routinely screened for in patients with polyposis. Here we describe a case with a mutation in MYH that has never been reported resulting in MYH-associated polyposis. MYH-associated polyposis is now known to be a cause of colorectal cancer. Our patient had a polyposis syndrome consistent with MYHassociated polyposis and the mutation of deletion of exon 7 in MYH is a novel mutation that would have otherwise been missed if the full MUTYH was not sequenced. Therefore, in patients with a suspicion of MYH associated polyposis that test negative for APC gene should be considered for complete MYH gene analysis.