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Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype–genotype correlations in Beckwith–Wiedemann syndrome
  1. F R Grati1,*,
  2. L Turolla2,*,
  3. P D’Ajello3,
  4. A Ruggeri1,
  5. M Miozzo4,
  6. G Bracalente5,
  7. D Baldo2,
  8. L Laurino4,
  9. R Boldorini7,
  10. E Frate2,
  11. N Surico3,
  12. L Larizza4,
  13. F Maggi1,
  14. G Simoni1
  1. 1Unita’ di Citogenetica e Biologia Molecolare, Laboratorio TOMA, Busto Arsizio, Varese, Italy
  2. 2Ambulatorio di Genetica Medica, Azienda ULSS 9 di Treviso, Italy
  3. 3Clinica Ostetrica e Ginecologica, Dipartimento di Medicina Clinica e Sperimentale, Università del Piemonte Orientale, Novara, Italy
  4. 4Cattedra di Genetica Medica, Dip. Medicina, Chirurgia e Odontoiatria, Università di Milano, Milano, Italy
  5. 5Unita’ Operativa di Ostetricia e Ginecologia, Azienda ULSS 9 di Treviso, Treviso, Italy
  6. 6Unità Operativa di Anatomia, Istologia Patologica, Citodiagnostica e Citogenetica, Azienda ULSS 9 di Treviso, Treviso, Italy
  7. 7Dipartimento di Medicina Sperimentale, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale, Novara, Italy
  1. Correspondence to:
 Dr F R Grati
 TOMA Advanced Biomedical Assays, SpA, Via Ferrer 25/27, 21052 Busto Arsizio (Varese), Italy; fgrati{at}


Background: The phenotypic variability in Beckwith–Wiedemann syndrome (BWS) reflects the genetic heterogeneity of the mechanism which by default leads to the deregulation of genes located at 11p15.5. Genotype–phenotype correlation studies have demonstrated an association between omphalocoele and CDKN1C/p57 mutations or hypermethylation. Paternal uniparental disomy 11 (pUPD11) has been described only in the mosaic condition with both uniparental and biparental cell lines, and no association with omphalocoele has been pointed out.

Methods: Two cases are presented here, in which a paternal segmental UPD11 was detected by molecular investigation of amniotic fluid cell cultures after the presence of apparently isolated omphalocoele was revealed in the fetuses by ultrasound scan. Further studies were performed on additional autoptic feto-placental tissues to characterise the distribution of the uniparental cell line and to unmask any biparental lineage in order to document in more detail the as yet unreported association between omphalocoele and pUPD11.

Results: Results on the UPD distribution profile showed that the abdominal organs have a predominant uniparental constitution. This condition could mimic the effect of CDKN1C/p57 inactivation, causing the omphalocoele.

Conclusion: New genotype–phenotype correlations emerge from the investigated cases, suggesting that molecular analysis be extended to all cases with fetal omphalocoele in order to establish the incidence of pUPD11 in complete BWS and in monosymptomatic/mild forms.

  • AF, amniotic fluid
  • BWS, Beckwith–Wiedemann syndrome
  • CNS, central nervous system
  • CDKN1C, cyclin-dependent kinase inhibitor 1C
  • FISH, fluorescence in situ hybridisation
  • KCNQ1, potassium voltage-gated channel, subfamily Q, member 1
  • IGF2, insulin-like growth factor 2
  • MCC, maternal cell contamination
  • pUPD, paternal uniparental disomy
  • QF-PCR, quantitative fluorescent PCR
  • STR, short tandem repeat
  • US, ultrasound
  • wg, weeks of gestation

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  • * These authors contributed equally to this work.

  • Published Online First 26 January 2007

  • Competing interests: None declared.

    Parental/guardian informed consent was obtained for publication of figures 1 and 2.