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Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism
  1. Valeria Romanelli1,2,
  2. Julián Nevado1,2,
  3. Mario Fraga3,
  4. Alex Martín Trujillo4,
  5. Maria Ángeles Mori1,2,
  6. Luis Fernández1,2,
  7. Guiomar Pérez de Nanclares5,6,
  8. Víctor Martínez-Glez1,2,
  9. Guillermo Pita7,
  10. Heloisa Meneses1,2,8,
  11. Ricardo Gracia9,
  12. Sixto García-Miñaur1,2,
  13. Purificación García de Miguel10,
  14. Beatriz Lecumberri11,
  15. José Ignacio Rodríguez12,
  16. Anna González Neira7,
  17. David Monk4,
  18. Pablo Lapunzina1,2,13
  1. 1INGEMM, Instituto de Genética Médica y Molecular, IDIPAZ-Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  2. 2CIBERER, U753-Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain
  3. 3Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid, Madrid, Spain
  4. 4Cancer Epigenetic and Biology Program (PEBC), Institut D'Investigació Biomedica de Bellvitge (IDIBELL), Hospital Duran i Reynals, Barcelona, Spain
  5. 5Laboratorio de Genética Molecular, Unidad de Investigación, Hospital de Txagorritxu, Vitoria, Spain
  6. 6CIBERER, U725A- Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain
  7. 7CNIO, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
  8. 8Department of Genetics, Universidad Federal de Rio de Janeiro, Brazil
  9. 9Servicio de Endocrinología Infantil, IDIPAZ, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  10. 10Servicio de Oncología Pediátrica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  11. 11Servicio de Endocrinología, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  12. 12Departamento de Anatomía Patológica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  13. 13RESSC, Registro Español de Síndromes de Sobrecrecimiento, Madrid, Spain
  1. Correspondence to Pablo Lapunzina, INGEMM (Instituto de Genética Médica y Molecular), IdiPAZ Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain; plapunzina.hulp{at}salud.madrid.org

Abstract

Molecular studies in a patient with Beckwith–Wiedemann syndrome phenotype who developed two different tumours revealed an unexpected observation of almost complete loss of heterozygosity of all chromosomes. It is shown, by means of numerous molecular methods, that the absence of maternal contribution in somatic cells is due to high-degree (∼85%) genome-wide paternal uniparental disomy (UPD). The observations indicate that the genome-wide UPD results from diploidisation, and have important implications for genetic counselling and tumour surveillance for the growing number of UPD associated imprinting disorders.

  • Beckwith-Wiedemann syndrome
  • paternal uniparental disomy
  • diploidization
  • imprinting
  • endocrinology
  • clinical genetics
  • molecular genetics

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Footnotes

  • Funding Supported by Grant from the FIBHULP to Julian Nevado and by Grant from the FIS 08/1360 to Valeria Romanelli and Pablo Lapunzina.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Institutional Research Ethics Board of Hospital Universitario La Paz (#CEIC-HULP-PI-446).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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