Epigenetic profiling of the H19 differentially methylated region and comprehensive whole genome array-based analysis in Silver-Russell syndrome

Shin Yu Lin, Chien Nan Lee, Chia Cheng Hung, Wen Yu Tsai, Shuan Pei Lin, Ni Chung Li, Wu Shiun Hsieh, Yi Ching Tung, Dau Ming Niu, Wen Ming Hsu, Lang Yao Chen, Mei Ya Fang, Mei Pin Tu, Pei Wen Kuo, Chiou Ya Lin, Yi Ning Su, Hong Nerng Ho

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous congenital disorder characterized by severe growth retardation. Hypomethylation of the differentially methylated region (DMR) of the H19 gene and uniparental disomy of maternal chromosome 7 is present in ̃45% of the patients with SRS so more than half of these patients have no known genetic etiology. We combined several molecular technologies including multiplex methylation polymerase chain reaction, methylation-sensitive multiple ligation probe-dependent amplification, and methylation-sensitive high-resolution melting to assess the epigenetic status of 34 patients with SRS. Additionally, we applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Thirteen patients (38.2%) had hypomethylation of the DMR of the H19 gene and none had uniparental disomy of maternal chromosome 7. The whole genome arrays identified five patients (14.7%) with microdeletions on chromosomes 1q23q24.3, 7p15.3, 13q31.3, 14q32.31, and 15q26.2qter, respectively. The overall mutation detection rate was 52.9% by the epigenetic study and the whole genome strategy. Although epimutation may be the major cause of SRS and can be identified by multiplex methylation polymerase chain reaction, the whole genome approach also provides information on the etiology of SRS. If no epimutation is identified in the patients with typical SRS, microdeletions should be suspected.

Original languageEnglish
Pages (from-to)2521-2528
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume152 A
Issue number10
DOIs
Publication statusPublished - Oct 1 2010
Externally publishedYes

Keywords

  • Array CGH
  • H19 gene
  • Microdeletion
  • Silver-Russell syndrome
  • UPD(7)mat

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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