Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98.

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

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.

Afiliación

Thibodeau ML; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.

Cytogenet Genome Res ; 152(3): 117-121, 2017.

Article en En | MEDLINE | ID: mdl-28854430

RESUMEN

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;q15). 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 11p 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 12p12.1, 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.

Asunto(s)

Angiomiolipoma/genética; Cromosomas Humanos Par 11/genética; Cromosomas Humanos Par 12/genética; Neoplasias Renales/genética; Proteínas de Complejo Poro Nuclear/genética; Translocación Genética; Adulto; Amniocentesis; Análisis Citogenético/métodos; Femenino; Proteínas Ligadas a GPI/genética; Estudio de Asociación del Genoma Completo; Genómica/métodos; Humanos; Péptidos y Proteínas de Señalización Intercelular/genética; Proteínas de Neoplasias/genética; Regiones Promotoras Genéticas; Seudogenes; Sitio de Iniciación de la Transcripción; Esclerosis Tuberosa/diagnóstico; Esclerosis Tuberosa/genética

Palabras clave

Balanced translocation; Pseudogene; Renal angiomyolipomas; Tuberous sclerosis; Whole-genome sequencing

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Translocación Genética / Cromosomas Humanos Par 11 / Cromosomas Humanos Par 12 / Angiomiolipoma / Proteínas de Complejo Poro Nuclear / Neoplasias Renales Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Cytogenet Genome Res Asunto de la revista: GENETICA Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza

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