Lirussi Frédéric, Jonard Laurence, Gaston Véronique, Sanlaville Damien, Kooy R Frank, Winnepenninckx Birgitta, Maher Eamonn R, Fitzpatrick David R, Gicquel Christine, Portnoï Marie-France, Couderc Rémy, Vazquez Marie-Paule, Bahuau Michel
Service de Biochime et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, AP-HP, Paris, France.
Am J Med Genet A. 2007 Dec 1;143A(23):2796-803. doi: 10.1002/ajmg.a.31768.
Beckwith-Wiedemann syndrome (BWS) is an overgrowth condition with tumor proclivity linked to a genetic imbalance of a complex imprinted region in 11p15.5. A female child with features fitting in with the BWS diagnostic framework and an apparent loss of imprinting (LOI) of the IGF2 gene in 11p15.5 was also reported to have a de novo chromosome 18q segmental deletion (Patient 1), thus pointing at the location of a possible trans-activating regulator element for maintenance of IGF2 imprinting and providing one of the few examples of locus heterogeneity of BWS. A second child with de novo 18q23 deletion and features of macroglossia, naevus flammeus, bilateral inguinal hernia and transient neonatal hypoglycemia, thus also fitting in with the BWS diagnostic framework, is here fully reported (Patient 2). In this child, an analysis of the BWS1 locus precluded any paternal isodisomy and showed a normal imprinting pattern (mono-allelic expression of IGF2 and normal H19 and CDKN1OT1/LIT1 methylation index). In Patients 1 and 2, deletions were shown to overlap, defining a minimal region of haplo-insufficiency of 3.8-5.6 Mb in 18q23. We conclude that this region provides a candidate location for an original macroglossia condition with strong overlap with BWS, but without obvious upstream functional relationship with the BWS1 locus in 11p15.5. Because this minimal region of haplo-insufficiency falls into a common region of deletion in 18q- syndrome, we inferred that this macroglossia condition would follow a recessive pattern of inheritance.
贝克威思-维德曼综合征（BWS）是一种过度生长疾病，具有肿瘤倾向，与11p15.5复杂印记区域的基因失衡有关。据报道，一名具有符合BWS诊断框架特征且11p15.5中IGF2基因明显印记丢失（LOI）的女童还存在18号染色体q臂节段性新发缺失（患者1），这指出了一个可能维持IGF2印记的反式激活调节元件的位置，并提供了BWS基因座异质性的少数例子之一。本文全面报道了第二名患有18q23新发缺失且具有巨舌、焰色痣、双侧腹股沟疝和短暂性新生儿低血糖特征的儿童，因此也符合BWS诊断框架（患者2）。在这名儿童中，对BWS1基因座的分析排除了任何父源同二体，并显示出正常的印记模式（IGF2单等位基因表达以及正常的H19和CDKN1OT1/LIT1甲基化指数）。在患者1和患者2中，缺失区域显示有重叠，确定了18q23中3.8 - 5.6 Mb的单倍体不足最小区域。我们得出结论，该区域为一种与BWS有强烈重叠但与11p15.5中的BWS1基因座无明显上游功能关系的原发性巨舌症提供了一个候选位置。由于这个单倍体不足最小区域位于18q - 综合征常见的缺失区域，我们推断这种巨舌症将遵循隐性遗传模式。
