Different methylation patterns in BWS/SRS cases clarified by MS-MLPA

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• 作者：Mihaela Lukova (1) (2)
  Albena Todorova (1) (2)
  Tihomir Todorov (2)
  Vanyo Mitev (1)
  
• 关键词：MS ; MLPA ; Beckwith ; Wiedemann syndrome (BWS) ; Silver–Russell syndrome (SRS) ; 11p15 ; KvDMR ; H19DMR
• 刊名：Molecular Biology Reports
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：40
• 期：1
• 页码：263-268
• 全文大小：466KB
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• 作者单位：Mihaela Lukova (1) (2)
  Albena Todorova (1) (2)
  Tihomir Todorov (2)
  Vanyo Mitev (1)
  
  1. Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 “Zdrave-Street, 1431, Sofia, Bulgaria
  2. Genetic Medico-Diagnostic Laboratory “Genica- Sofia, Bulgaria
  
• ISSN：1573-4978

文摘

Molecular abnormalities in the 11p15.5 imprinted gene cluster lead to two different growth diseases: Beckwith-Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS). They are mainly caused by epigenetic alterations in one of the two imprinting 11p15 control regions (ICR1 and ICR2). These CpG-rich regions are differentially methylated on the maternally and paternally derived chromosomes. We report four different methylation patterns along the BWS/SRS critical region, clarified by methylation-specific multiplex ligation-dependent probe amplification. The mathematical processing of the data provides information about alterations in the methylation status: from hypo- to almost complete demethylation of KvDMR, hypo- and hypermethylation of H19DMR and combined results from both regions provide information on paternal uniparental disomy (patUPD). The study concerns two BWS cases with KvDMR hypomethylation and almost complete loss of methylation, respectively; two patUPD11p15 cases with H19DMR hypermethylation/KvDMR hypomethylation, and one SRS case with H19DMR demethylation. In some cases KvDMR hypomethylation in patUPD11p15 can be difficult to assess, which requires combination with STR analysis or alternative method. The STR analysis provides also information on complete or segmental coverage and iso- or heterodisomy. Following this systematic approach, the precise diagnosis can be clarified in a few days and different methylation patterns could be detected.