title: Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype-genotype correlations in Beckwith-Wiedemann syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unita' di Citogenetica e Biologia Molecolare, Laboratorio TOMA, Busto Arsizio, Varese, Italy. fgrati@tomalab.com
authors.forename: F R
authors.initials: FR
authors.lastname: Grati
authors.forename: L
authors.initials: L
authors.lastname: Turolla
authors.forename: P
authors.initials: P
authors.lastname: D'Ajello
authors.forename: A
authors.initials: A
authors.lastname: Ruggeri
authors.forename: M
authors.initials: M
authors.lastname: Miozzo
authors.forename: G
authors.initials: G
authors.lastname: Bracalente
authors.forename: D
authors.initials: D
authors.lastname: Baldo
authors.forename: L
authors.initials: L
authors.lastname: Laurino
authors.forename: R
authors.initials: R
authors.lastname: Boldorini
authors.forename: E
authors.initials: E
authors.lastname: Frate
authors.forename: N
authors.initials: N
authors.lastname: Surico
authors.forename: L
authors.initials: L
authors.lastname: Larizza
authors.forename: F
authors.initials: F
authors.lastname: Maggi
authors.forename: G
authors.initials: G
authors.lastname: Simoni
mesh_terms: D000025:Abortion, Eugenic; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology; D001506:Beckwith-Wiedemann Syndrome / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006554:Hernia, Umbilical / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007621:Karyotyping; D018895:Microsatellite Repeats; D010641:Phenotype; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D024182:Uniparental Disomy / Q000235:genetics*