Identification of Lynch syndrome risk variants in the Romanian population

• DOI: 10.1111/jcmm.13881
• Publication Date: 2018-10-16T07:58:40Z
• Authors: Paul D. Iordache; Dana Mates; Bjarni Gunnarsson; Hannes P. Eggertsson; Patrick Sulem; Stefania Benonisd...; Irma Eva Csiki; Stefan Rascu; Daniel Radavoi; Radu Ursu; Catalin Staicu; Violeta Calota; Angelica Voinoiu; Mariana Jinga; Gabriel Rosoga; Razvan Danau; Sorin Cristian Sima; Daniel Badescu; Nicoleta Suciu; Viorica Radoi; Ioan Nicolae Mates; Mihai Dobra; Camelia Nicolae; Sigrun Kristjansd...; Jon G. Jonasson; Andrei Manolescu; Gudny Arnadottir; Brynjar Jensson; Aslaug Jonasdottir; Asgeir Sigurdsson; Louise le Roux; Hrefna Johannsdottir; Thorunn Rafnar; Bjarni V. Halldor...; Viorel Jinga; Kari Stefansson
• Keywords: PMS2; MSH6; Lynch Syndrome; MLH1; MUTYH; MSH2

Abstract Two familial forms of colorectal cancer ( CRC ), Lynch syndrome LS ) and adenomatous polyposis FAP are caused by rare mutations in DNA mismatch repair genes MLH 1 , MSH 2 6 PMS the APC MUTYH respectively. No information is available on presence high‐risk Romanian population. We performed whole‐genome sequencing 61 cases with a family history and/or early onset disease, focusing analysis candidate variants genes. The frequencies all were assessed cohort 688 4567 controls. Immunohistochemical IHC staining for was tumour tissue. identified 11 cases; six one three . Combining predicted impact proteins, results previous reports, we found novel pathogenic :p.Lys84ThrfsTer4, :p.Ala586CysfsTer7, :p.Arg211ThrfsTer38), two that unlikely to be pathogenic. Also, confirmed previously published suggest reclassify reported variant uncertain significance :c.1559‐1G>C).