Monozygotic female twins discordant for Silver-Russell syndrome and hypomethylation of the H19-DMR

Kazuki Yamazawa, Masayo Kagami, Maki Fukami, Keiko Matsubara, Tsutomu Ogata

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41 Citations (Scopus)


Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and is frequently caused by hypomethylation of the paternally derived H19-DMR (epimutation). We observed 5 8/12-year-old female twins discordant for SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and bilateral fifth finger clinodactyly, whereas the other twin showed apparently normal phenotype. Microsatellite analysis for 26 loci on multiple chromosomes showed monozygosity. Methylation analysis for the H19-DMR indicated epimutation in roughly half of cells in the affected twin and normal patterns in the unaffected twin and the parents. X-inactivation analysis revealed random X-inactivation with a nearly identical pattern between the twins. The discordant methylation pattern of the H19-DMR may primarily be due to a failure to maintain the DNA methyltransferase-1-dependent methylation imprint around the pre-implantation S phase, because such failure would result in the production of two different cell clones, one with normally methylated DMR and the other with demethylated DMR, leading to the separation of cells with different characters and resultant twinning.

Original languageEnglish
Pages (from-to)950-955
Number of pages6
JournalJournal of Human Genetics
Issue number10
Publication statusPublished - 2008 Oct


  • DNMT1
  • Discordance
  • H19-DMR
  • Methylation
  • Monozygotic twin
  • Silver-Russell syndrome
  • X-inactivation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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