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01-03-2014 | Original Article

Lynch Syndrome in high risk Ashkenazi Jews in Israel

Authors: Yael Goldberg, Inbal Kedar, Revital Kariiv, Naama Halpern, Morasha Plesser, Ayala Hubert, Luna Kaduri, Michal Sagi, Israela Lerer, Dvorah Abeliovich, Tamar Hamburger, Aviram Nissan, Hanoch Goldshmidt, Irit Solar, Ravit Geva, Hana Strul, Guy Rosner, Hagit Baris, Zohar Levi, Tamar Peretz

Published in: Familial Cancer | Issue 1/2014

Abstract

Lynch Syndrome is caused by mutations in DNA mismatch repair genes. Diagnosis is not always trivial and may be costly. Information regarding incidence, genotype-phenotype correlation, spectrum of mutations and genes involved in specific populations facilitate the diagnostic process and contribute to clinical work-up. To report gene distribution, mutations detected and co-occurrence of related syndromes in a cohort of Ashkenazi Jews in Israel. Patients were identified in dedicated high risk clinics in 3 medical centers in Israel. Diagnostic process followed a multi-step scheme. It included testing for founder mutations, tumor testing, gene sequencing and MLPA. Lynch Syndrome was defined either by positive mutation testing, or by clinical criteria and positive tumor analysis. We report a cohort of 75 Ashkenazi families suspected of Lynch Syndrome. Mutations were identified in 51/75 (68 %) families: 38 in MSH2, 9 in MSH6, and 4 in MLH1. 37/51 (73 %) of these families carried one of the 3 ‘Ashkenazi’ founder mutations in MSH2 or MSH6. Each of the other 14 families carried a private mutation. 3 (6 %) were large deletions. Only 20/51 (39 %) families were Amsterdam Criteria positive; 42 (82 %) were positive for the Bethesda guidelines and 9 (18 %) did not fulfill any Lynch Syndrome criteria. We report C-MMRD and co-occurrence of BRCA and Lynch Syndrome in our cohort. Mutation spectra and gene distribution among Ashkenazi Jews are unique. Three founder Lynch Syndrome mutations are found in 73 % families with known mutations. Among the three, MSH2 and MSH6 are the most common. These features affect the phenotype, the diagnostic process, risk estimation, and genetic counseling.

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Title: Lynch Syndrome in high risk Ashkenazi Jews in Israel
Authors: Yael Goldberg
Inbal Kedar
Revital Kariiv
Naama Halpern
Morasha Plesser
Ayala Hubert
Luna Kaduri
Michal Sagi
Israela Lerer
Dvorah Abeliovich
Tamar Hamburger
Aviram Nissan
Hanoch Goldshmidt
Irit Solar
Ravit Geva
Hana Strul
Guy Rosner
Hagit Baris
Zohar Levi
Tamar Peretz
Publication date: 01-03-2014
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 1/2014
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-013-9675-2

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