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- Title
Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98.
- Authors
Thibodeau, My Linh; Steinraths, Michelle; Brown, Lindsay; Zong, Zheyuan; Shomer, Naomi; Taubert, Stefan; Mungall, Karen L.; Ma, Yussanne P.; Mueller, Rosemary; Birol, Inanc; Lehman, anna
- Abstract
A 41-year-old Asian woman with bilateral renal angiomyolipomas (AML) was incidentally identified to have a balanced translocation, 46,XX,t(11; 12)(p15.4;q 15). She had no other features or family history to suggest a diagnosis of tuberous sclerosis. Her healthy daughter had the same translocation and no renal AML at the age of 3 years. Whole-genome sequencing was performed on genomic maternal DNA isolated from blood. A targeted de novo assembly was then conducted with ABySS for chromosomes 11 and 12. Sanger sequencing was used to validate the translocation breakpoints. As a result, genomic characterization of chromosomes 11 and 12 revealed that the 11 p breakpoint disrupted the NUP98 gene in intron 1, causing a separation of the promoter and transcription start site from the rest of the gene. The translocation breakpoint on chromosome 12q was located in a gene desert. NUP98 has not yet been associated with renal AML pathogenesis, but somatic NUP98 alterations are recurrently implicated in hematological malignancies, most often following a gene fusion event. We also found evidence for complex structural events involving chromosome 12, which appear to disrupt the TDG gene. We identified a TDGP1 partially processed pseudogene at 12p 12.1, which adds complexity to the de novo assembly. In conclusion, this is the first report of a germline constitutional structural chromosome rearrangement disrupting NUP98 that occurred in a generally healthy woman with bilateral renal AML.
- Subjects
GENOMICS; TUBEROUS sclerosis; GENETIC testing; GENES; HUMAN genome
- Publication
Cytogenetic & Genome Research, 2017, Vol 152, Issue 3, p117
- ISSN
1424-8581
- Publication type
Article
- DOI
10.1159/000479463