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Beckwith–Wiedemann‐like macroglossia and 18q23 haploinsufficiency
Author(s) -
Lirussi Frédéric,
Jonard Laurence,
Gaston Véronique,
Sanlaville Damien,
Kooy R. Frank,
Winnepenninckx Birgitta,
Maher Eamonn R.,
FitzPatrick David R.,
Gicquel Christine,
Portnoï MarieFrance,
Couderc Rémy,
Vazquez MariePaule,
Bahuau Michel
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31768
Subject(s) - macroglossia , haploinsufficiency , locus (genetics) , imprinting (psychology) , beckwith–wiedemann syndrome , genetics , genomic imprinting , biology , chromosomal region , gene , medicine , dna methylation , phenotype , gene expression , pathology , tongue
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, nævus 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. © 2007 Wiley‐Liss, Inc.