MUTYH Associated Polyposis in the Non-Jewish Population in Northern Israel

Gili Reznick-Levi1, Itai Maza2, Nitzan Sharon Swartzman1, Adi Mori1, Hagit Baris-Feldman and 1, Elizabeth Half-Onn2

1Genetic Institute, Rambam Health Care Campus, Haifa, Israel. 2Gastroenterology., Institute Rambam Health Care Campus , Haifa, Israel


Genetic diagnosis of MUTYH  Polyposis in Israel has focused on the two common Caucasian founder mutations frequent in the Israeli North Africa Jewish population. Utilization of Next Generation Sequencing revealed rare/new variants.
Aim: to evaluate the spectrum of MYH mutations in the Non-Jewish polyposis population (NJPP) in Northern Israel.

Methods: During 2013-2019, all consecutive NJPP fulfilling clinical criteria of the Israeli Genetic Society (>20 polyps, or >15 polyps with parental consanguinity, or >10 polyps and CRC( were offered sequencing for APC and MUTYH genes.

Results: 22 patients (19 families) underwent genetic testing. Eight patients from five families (5/19 families 26.3%) carried bialleic pathogenic variants in MUTYH (p.Glu480del, p.His85Arg, p.Tyr84*). None of the mutations were the common Caucasian founder mutations. The p.Glu480del was found in four unrelated patients (two Muslim Arabs and two Druze) from two different villages. p.Glu480del and p.His85Arg have been previously reported in MAP patients; however, p.Tyr84* is a novel variant.
None of these Biallelic MYH carriers had extracolonic cancers except for one having  both liposarcoma and papillary thyroid cancers. None of the Cristian Arab patients (six) were found to carry any mutation in MUTYH.

Conclusion: The pathogenic variant MUTYH detection rate in the NJPP in Northern Israel is 26.3%. The spectrum of the mutations in this population differs from the general Israeli Jewish population. The variant p.Glu480del may be a founder mutation in the Muslim Arab and Druze populations. These results may help guide the polyposis and colorectal cancer gene testing strategy in the NJPP in Israel.