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Beckwith–Wiedemann syndrome
Author(s) -
Choufani Sanaa,
Shuman Cheryl,
Weksberg Rosanna
Publication year - 2010
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.30267
Subject(s) - beckwith–wiedemann syndrome , genomic imprinting , imprinting (psychology) , epigenetics , genetics , biology , gene , untranslated region , gene expression , messenger rna , dna methylation
Abstract Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. Approximately 85% of reported BWS cases are sporadic, while the remaining 15% are familial. BWS is caused by epigenetic or genomic alterations which disrupt genes in one or both of the two imprinted domains on chromosome 11p15.5. In each domain, an imprinting center regulates the expression of imprinted genes in cis . Normally in domain 1, insulin‐like growth factor 2 ( IGF2 ) and the untranslated mRNA H19 are monoallelically expressed. In BWS, increased expression of IGF2 occurs via several mechanisms. In domain 2, CDKN1C , a growth repressor, and an untranslated RNA, KCNQ1OT1 , are normally expressed monoallelically. In cases of BWS, several mechanisms result in reduced expression of CDKN1C . Recent reports of BWS cases have identified mutations outside the chromosome 11p15.5 critical region, thereby broadening the challenges in the diagnosis and genetic counseling of individuals and families with BWS. © 2010 Wiley‐Liss, Inc.