BRCA2 founder mutation in Slovenian breast cancer families

Krajc, Mateja; Grève, Jacques De; Goelen, Guido; Teugels, Erik

doi:10.1038/sj.ejhg.5200886

Cited by 18 publications

(24 citation statements)

References 11 publications

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“…A BRCA2 gene mutation was found in four patients: in three patients, we detected the Slovenian founder mutation IVS16-2A>G (Krajc et al, 2002), and in the fourth, the 4206insA mutation was found. Two carriers of the Slovenian founder mutation were brothers.…”

Section: Resultsmentioning

confidence: 81%

“…In 2002, we reported the BRCA2 mutation IVS16-2A>G as a highly recurrent founder mutation in Slovenian breast cancer families (Krajc et al, 2002). According to the BIC database (Breast Cancer Information Core Internet Website, 2005), this mutation was reported worldwide only three times, twice by Myriad in ''Western Europeans'' and once by Santarosa from Aviano in Italy (Santarosa et al, 1999), a city close to Slovenian border.…”

Section: Discussionmentioning

confidence: 99%

“…In families with three cases of breast cancer or with one ovarian cancer and at least one breast cancer, all remaining small exons as well as the extremities of the large exons were further analyzed by DGGE. The presence of the Slovenian founder mutation IVS16-2A>G in the BRCA2 gene (Krajc et al, 2002) was confirmed by the Immunology Laboratory at the Institute of Oncology Ljubljana using a PCR-based method for rapid detection of highly recurrent mutations. One of the primers was specifically modified in order to create a specific restriction site in the wild-type PCR fragment, not present in the mutant allele.…”

Section: Methodsmentioning

confidence: 96%

“…Because of very limited funds for our study, we made a compromise in the laboratory tests that were performed. Therefore, the DNA samples from sporadic MBC patients were screened only for four highly recurrent mutations previously identified in the Slovenian population (Krajc et al, 2002(Krajc et al, , 2007. The denaturing gradient gel electrophoresis (DGGE) analysis (van der Hout et al, 2006) of these four representative PCR fragments (exons 5 and 20 from BRCA1, exon 17 from BRCA2, and a fragment of BRCA1 exon 11 harboring the 1806C>T mutation) leads to the detection of breast cancer predisposing mutations in 68% of the Slovenian BRCA1=2 families (Krajc et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

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BRCA2 Gene Mutations in Slovenian Male Breast Cancer Patients

et al. 2008

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Male breast cancer (MBC) is a rare disease, comprising less than 1% of breast cancer patients in Slovenia. Some inherited cases are due to the mutations of BRCA1 or BRCA2 genes. There is no information available about the frequency of BRCA gene mutations in Slovenian MBC population. The purpose of this study was to characterize BRCA germline mutations in Slovenian MBC patients. Forty-one patients who were diagnosed with breast cancer at the Institute of Oncology Ljubljana between 1970 and 2006 were proposed to take part in this study. Of them, 27 agreed to follow a genetic counseling session and 25 patients agreed to provide a blood sample for genetic testing. The BRCA1 and BRCA2 genes from the MBC patients were screened for four highly recurrent mutations in the Slovenian population. When an additional breast cancer case or an ovarian cancer was present in the family, a more extended analysis was performed. No BRCA1 mutations were found. A BRCA2 gene mutation was identified in four MBC patients. Three of them carried the Slovenian founder mutation IVS16-2A>G. All four mutations were confined to the patients with a family history of breast cancer. Among the MBC patients with a family history of breast cancer in the first- or second-degree relatives, the frequency of BRCA2 gene mutation was 50%. The median age of the patients with a BRCA2 gene mutation was 60 years, not significantly different from those without a mutation. The BRCA2 mutations were diagnosed in 16% of our MBC patients.

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Section: Resultsmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

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BRCA2 Gene Mutations in Slovenian Male Breast Cancer Patients

et al. 2008

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“…mutations descending from a single ancestor have been described for example in genes causing familial breast cancer. [47][48][49][50][51] Chondrocytic cell lines were not available for the predictions of the promoter and enhancer regions. Instead data from HSMM and GM12878 cell lines were used.…”

Section: Discussionmentioning

confidence: 99%

A Whole Exome Study Identifies Novel Candidate Genes for Vertebral Bone Marrow Signal Changes (Modic Changes)

Kraatari

Skarp

Niinimäki

et al. 2017

Spine

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Study Design. Family-based study Objective. To identify rare genetic factors predisposing to Modic changes (MC).Summary of Background Data. Lumbar disc degeneration (LDD) is one of the contributing factors behind low back pain (LBP). Lumbar MC visualized as bone marrow signal intensity changes on magnetic resonance imaging (MRI) represent a specific phenotype of LDD, which has stronger association with LBP than LDD without MC.Methods. The study set consisted of two Finnish families: Family I included seven affected and four unaffected individuals and Family II eight affected and seven unaffected individuals. MC were evaluated in 26 individuals using MRI. Whole exome sequencing was used to identify alleles co-segregating with MC. ANNOVAR was used to carry out functional annotation of alleles and their frequencies were evaluated using 1000Genomes, Sequencing Initiative Suomi (SISu) and the Exome Aggregation Consortium (ExAC) databases.Results. We identified predisposing genetic alleles for MC in two Finnish families. In each family only single allele co-segregated with MC. In Family I the observed allele was an insertion and deletion in the HSPG2 gene, resulting in a premature termination codon. In Family II a single nucleotide polymorphism (rs61753465) in the MAML1 gene was identified in all affected family members.Conclusions. We have identified two novel candidate genes, MAML1 and HSPG2, associating with MC. These genes are important in cartilage structure and joint cartilage maintenance. Our findings are novel among lumbar spine degenerative phenotypes.3

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Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants

Vallée¹,

Sera

Nix

et al. 2016

Human Mutation

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Clinical mutation screening of the cancer susceptibility genes BRCA1 and BRCA2 generates many Unclassified Variants (UVs). Most of these UVs are either rare missense substitutions or nucleotide substitutions near the splice junctions of the protein coding exons. Previously, we developed a quantitative method for evaluation of BRCA gene UVs – the “integrated evaluation” – that combines a sequence analysis-based prior probability of pathogenicity with patient and/ or tumor observational data to arrive at a posterior probability of pathogenicity. One limitation of the sequence analysis-based prior has been that it evaluates UVs from the perspective of missense substitution severity but not probability to disrupt normal mRNA splicing. Here, we calibrated output from the splice site fitness program MaxEntScan to generate spliceogenicity-based prior probabilities of pathogenicity for BRCA gene variants; these range from 0.97 for variants with high probability to damage a donor or acceptor to 0.02 for exonic variants that do not impact a splice junction and are unlikely to create a de novo donor. We created a database http://priors.hci.utah.edu/PRIORS/ that provides the combined missense substitution severity and spliceogenicity-based probability of pathogenicity for BRCA gene single nucleotide substitutions. We also updated the BRCA gene Ex-UV LOVD, available at http://hci-exlovd.hci.utah.edu, with 77 re-evaluable variants.

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BRCA2 founder mutation in Slovenian breast cancer families

Cited by 18 publications

References 11 publications

BRCA2 Gene Mutations in Slovenian Male Breast Cancer Patients

BRCA2 Gene Mutations in Slovenian Male Breast Cancer Patients

A Whole Exome Study Identifies Novel Candidate Genes for Vertebral Bone Marrow Signal Changes (Modic Changes)

Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants

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