https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45052 MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.]]> Wed 26 Oct 2022 11:45:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10386 Wed 11 Apr 2018 17:00:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:458 Wed 11 Apr 2018 15:11:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1099 Wed 11 Apr 2018 09:53:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27793 BRCA1 there has only ever been described two bi-allelic mutation carriers, one of whom was subsequently shown to be a mono-allelic carrier. The second patient diagnosed with two BRCA1 mutations appears to be accurate but there remain some questions about the missense variant identified in that patient. In this report we have identified a woman who is a bi-allelic mutation carrier of BRCA1 and provide an explanation as to why this patient has a phenotype very similar to that of any mono-allelic mutation carrier. The splice variant identified in this patient appears to be associated with the up-regulation of a BRCA1 splice variant that rescues the lethality of being a double mutant. The consequences of the findings of this report may have implications for mutation interpretation and that could serve as a model for not only BRCA1 but also for other autosomal dominant disorders that are considered as being embryonically lethal.]]> Wed 06 Apr 2022 13:57:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30018 Tue 20 Sep 2022 14:49:52 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24811 Thu 27 Jan 2022 15:55:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14315 Sat 24 Mar 2018 08:24:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23143 Sat 24 Mar 2018 07:10:33 AEDT ]]>