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A case of Beckwith-Wiedemann syndrome caused by a cryptic 11p15 deletion encompassing the centromeric imprinted domain of the BWS locus.
  1. Marcella Zollino1,
  2. Daniela Orteschi1,
  3. Giuseppe Marangi1,
  4. Agostina De Crescenzo2,
  5. Vanna Pecile3,
  6. Andrea Riccio2,
  7. Giovanni Neri1,*
  1. 1 Istituto di Genetica Medica, Università Cattolica Sacro Cuore, Policlinico “A.Gemelli”, Roma, Italy;
  2. 2 Dipartimento di Scienze Ambientali, Seconda Università di Napoli, Caserta, Italy;
  3. 3 Unità di Citogenetica, IRCCS “Burlo Garofalo, Trieste, Italy
  1. Correspondence to: Giovanni Neri, Genetica Medica, Università Cattolica del S. Cuore, Istituto di Genetica Medica, Universita Cattolica, Largo F Vito 1, Roma, 00168, Italy; gneri{at}rm.unicatt.it

Abstract

Beckwith-Wiedemann syndrome is a clinically variable and genetically heterogeneous disorder, providing evidence that imprinted genes play key roles in the control of fetal growth. Clinically, diagnostic criteria include macrosomia, macroglossia, abdominal wall defects, neonatal hypoglycemia, visceromegalies and hemihyperplasia. Component clinical manifestations also include renal abnormalities, adrenocortical cytomegaly and a characteristic facial appearance, with midface hypoplasia and ear anomalies. Genetically, BWS is associated with disturbances within two different domains on 11p15 that are controlled by distinct Imprinting Control Regions, ICR1 and ICR2. The majority of patients have abnormalities within ICR2. In particular, loss of maternal methylation accounts for 50-60% of cases, and is associated with reduction in the expression of the CDKN1C gene, a member of the cyclin-dependent kinase inibitor family acting as negative regulator of cell proliferation. Mutations in CDKN1C are detected in another 5-10 % of subjects with sporadic BWS. Chromosome deletions affecting ICR2 are uncommon. We report on a patient with BWS in which a de novo 11p15 deletion was detected by array-CGH. The deletion, that was maternal in origin, encompassed ICR2 and several flanking genes, including CDKN1C. A normal methylation pattern of ICR1 was observed, supporting the model of two independent domains within the BWS locus.

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