@article{ZaumNandaKressetal.2022,
  author    = {Zaum, Ann-Kathrin and Nanda, Indrajit and Kress, Wolfram and Rost, Simone},
  title     = {Detection of pericentric inversion with breakpoint in DMD by whole genome sequencing},
  series = {Molecular Genetics \& Genomic Medicine},
  volume    = {10},
  journal   = {Molecular Genetics \& Genomic Medicine},
  number    = {10},
  doi       = {10.1002/mgg3.2028},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293940},
  year      = {2022},
  abstract  = {Background Dystrophinopathies caused by variants in the DMD gene are a well-studied muscle disease. The most common type of variant in DMD are large deletions. Very rarely reported forms of variants are chromosomal translocations, inversions and deep intronic variants (DIVs) because they are not detectable by standard diagnostic techniques (sequencing of coding sequence, copy number variant detection). This might be the reason that some clinically and histologically proven dystrophinopathy cases remain unsolved. Methods We used whole genome sequencing (WGS) to screen the entire DMD gene for variants in one of two brothers suffering from typical muscular dystrophy with strongly elevated creatine kinase levels. Results Although a pathogenic DIV could not be detected, we were able to identify a pericentric inversion with breakpoints in DMD intron 44 and Xq13.3, which could be confirmed by Sanger sequencing in the index as well as in his brother and mother. As this variation affects a major part of DMD it is most likely disease causing. Conclusion Our findings elucidate that WGS is capable of detecting large structural rearrangements and might be suitable for the genetic diagnostics of dystrophinopathies in the future. In particular, inversions might be a more frequent cause for dystrophinopathies as anticipated and should be considered in genetically unsolved dystrophinopathy cases.},
  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}
}
@article{WagenhaeuserRickertSommeretal.2022,
  author    = {Wagenh{\"a}user, Laura and Rickert, Vanessa and Sommer, Claudia and Wanner, Christoph and Nordbeck, Peter and Rost, Simone and {\"U}{\c{c}}eyler, Nurcan},
  title     = {X-chromosomal inactivation patterns in women with Fabry disease},
  series = {Molecular Genetics \& Genomic Medicine},
  volume    = {10},
  journal   = {Molecular Genetics \& Genomic Medicine},
  number    = {9},
  doi       = {10.1002/mgg3.2029},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312795},
  year      = {2022},
  abstract  = {Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45\%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25\% distribution) in 6/87 (7\%) mouth epithelial cell samples, 31/88 (35\%) blood samples, and 9/27 (33\%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.},
  language  = {en}
}