@article{SepahiFaustSturmetal.2019,
  author    = {Sepahi, Ilnaz and Faust, Ulrike and Sturm, Marc and Bosse, Kristin and Kehrer, Martin and Heinrich, Tilman and Grundman-Hauser, Kathrin and Bauer, Peter and Ossowski, Stephan and Susak, Hana and Varon, Raymonda and Schr{\"o}ck, Evelin and Niederacher, Dieter and Auber, Bernd and Sutter, Christian and Arnold, Norbert and Hahnen, Eric and Dworniczak, Bernd and Wang-Gorke, Shan and Gehrig, Andrea and Weber, Bernhard H. F. and Engel, Christoph and Lemke, Johannes R. and Hartkopf, Andreas and Huu Phuc, Nguyen and Riess, Olaf and Schroeder, Christopher},
  title     = {Investigating the effects of additional truncating variants in DNA-repair genes on breast cancer risk in BRCA1-positive women},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5946-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237676},
  year      = {2019},
  abstract  = {Background Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72\%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon. Methods We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways. Results Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00-27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2\%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6\%; 95\%-CI 24.7 - 47.7\%) compared to 16 women of controls (26.7\%; 95\%-CI 16.1 to 39.7\%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95\%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05. Conclusions To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-positive patients. Larger cohorts are needed to confirm these results.},
  language  = {en}
}
@article{PlutaHoffjanZimmeretal.2022,
  author    = {Pluta, Natalie and Hoffjan, Sabine and Zimmer, Frederic and K{\"o}hler, Cornelia and L{\"u}cke, Thomas and Mohr, Jennifer and Vorgerd, Matthias and Nguyen, Hoa Huu Phuc and Atlan, David and Wolf, Beat and Zaum, Ann-Kathrin and Rost, Simone},
  title     = {Homozygous inversion on chromosome 13 involving SGCG detected by short read whole genome sequencing in a patient suffering from limb-girdle muscular dystrophy},
  series = {Genes},
  volume    = {13},
  journal   = {Genes},
  number    = {10},
  issn      = {2073-4425},
  doi       = {10.3390/genes13101752},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288122},
  year      = {2022},
  abstract  = {New techniques in molecular genetic diagnostics now allow for accurate diagnosis in a large proportion of patients with muscular diseases. Nevertheless, many patients remain unsolved, although the clinical history and/or the muscle biopsy give a clear indication of the involved genes. In many cases, there is a strong suspicion that the cause must lie in unexplored gene areas, such as deep-intronic or other non-coding regions. In order to find these changes, next-generation sequencing (NGS) methods are constantly evolving, making it possible to sequence entire genomes to reveal these previously uninvestigated regions. Here, we present a young woman who was strongly suspected of having a so far genetically unsolved sarcoglycanopathy based on her clinical history and muscle biopsy. Using short read whole genome sequencing (WGS), a homozygous inversion on chromosome 13 involving SGCG and LINC00621 was detected. The breakpoint in intron 2 of SGCG led to the absence of γ-sarcoglycan, resulting in the manifestation of autosomal recessive limb-girdle muscular dystrophy 5 (LGMDR5) in the young woman.},
  language  = {en}
}