High prevalence of MUTYH associated polyposis among minority populations in Israel, due to rare founder pathogenic variants.

Autor: Reznick Levi G; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel. Electronic address: g_reznick@rambam.health.gov.il., Goldberg Y; Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Segev H; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel., Maza I; Gastroenterology Department, Rambam Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Gorelik Y; Gastroenterology Department, Rambam Medical Center, Haifa, Israel., Laish I; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Gastroenterology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel., Levi Z; Division of Gastroenterology, Rabin Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Kedar I; Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel., Naftali Nathan S; Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel., Sharon Swartzman N; Institute of Medical Genetics, Meir Medical Center, Kfar Saba, Israel., Abu Freha N; The Institute of Gastroenterology and Hepatology, Beer Sheva, Israel; Soroka University Medical Center, Faculty of Health Sciences, Beer Sheva, Israel., Paritsky M; Baruch Padeh Medical Center, Poriya, Israel; Faculty of Medicine, Bar Ilan University, Galilee, Israel., Rennert G; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center and Personalized Medicine Program, Haifa, Israel; Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel., Baris Feldman H; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel., Paperna T; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel., Weiss K; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Half EE; Gastroenterology Department, Rambam Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Jazyk: angličtina
Zdroj: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2023 Jul; Vol. 55 (7), pp. 880-887. Date of Electronic Publication: 2023 Feb 04.
DOI: 10.1016/j.dld.2023.01.151
Abstrakt: Background: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum.
Methods: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel.
Results: The Northern cohort included 37 patients from 30 unrelated families; 8(26.6%) carried bi-allelic MUTYH PVs. The major variant p.Glu452del was detected in 6/8 Druze and Muslim families who shared the same haplotype. Other PVs detected in both cohorts included p.Tyr56Ter, p.His57Arg, c.849+3A>C, p.Ala357fs, and p.Tyr151Cys. Among bi-allelic carriers, 88% reported consanguinity, and 100% had positive family history for polyposis or colorectal cancer (CRC). Generally, the age of CRC was 10 years younger than reported in the general MAP population.
Conclusions: MAP accounted for 27% of polyposis cases in the Arab population of Northern Israel. PVs spectrum is unique, with high frequency of the founder variant p.Glu452del. Our results may inform the genetic testing strategy in the Israeli Arab population.
Competing Interests: Conflict of interest No conflict of interest declared by the authors.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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