Journal Article

Discordant <i>KCNQ1OT1</i> imprinting in sets of monozygotic twins discordant for Beckwith–Wiedemann syndrome

Rosanna Weksberg, Cheryl Shuman, Oana Caluseriu, Adam C. Smith, Yan-Ling Fei, Joy Nishikawa, Tracy L. Stockley, Lyle Best, David Chitayat, Ann Olney, Elizabeth Ives, Adele Schneider, Timothy H. Bestor, Madeline Li, Paul Sadowski and Jeremy Squire

in Human Molecular Genetics

Volume 11, issue 11, pages 1317-1325
Published in print May 2002 | ISSN: 0964-6906
Published online May 2002 | e-ISSN: 1460-2083 | DOI:
Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith–Wiedemann syndrome

Show Summary Details


Beckwith–Wiedemann syndrome (BWS) presents with visceromegaly, macroglossia, tumor predisposition and other congenital abnormalities, and is usually associated with abnormalities of chromosome 11p15. A number of identical twin pairs, mostly female, have been reported to be discordant for BWS. We show here that the incidence of female monozygotic twins among patients with BWS is dramatically increased over that of the general population. A cluster of imprinted genes within 11p15 is thought to be coordinately regulated via the imprinted expression of KCNQ1OT1, which encodes an untranslated RNA. In skin fibroblasts from five monozygotic twin pairs discordant for BWS, each affected twin had an imprinting defect at KCNQ1OT1 on 11p15, whereas the unaffected twin did not. Five additional monozygotic twin pairs, for whom only blood was available, also displayed an imprinting defect at KCNQ1OT1. It is possible that discordance for BWS in MZ twins is due to unequal splitting of the inner cell mass during twinning, thereby causing differential maintenance of imprinting at KCNQ1OT1. Alternatively, we propose that KCNQ1OT1 is especially vulnerable to a loss of imprinting event, caused by a lack of maintenance DNA methylation at a critical stage of preimplantation development, and that this loss of imprinting predisposes to twinning as well as to discordance for BWS. These data underscore the importance of continued surveillance of children born following assisted reproductive technologies that impact the preimplantation embryo.

Journal Article.  6468 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.