Hypomethylation of the h19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype

被引:159
作者
Bliek, J
Terhal, P
van den Bogaard, MJ
Maas, S
Hamel, B
Salieb-Beugelaar, G
Simon, M
Letteboer, T
van der Smagt, J
Kroes, H
Mannens, M
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1100 DE Amsterdam, Netherlands
[2] Univ Utrecht, Dept Med Genet, Med Ctr, Utrecht, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands
[4] Erasmus Med Ctr, Dept Clin Genet, Rotterdam, Netherlands
关键词
D O I
10.1086/502981
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The H19 differentially methylated region ( DMR) controls the allele-specific expression of both the imprinted H19 tumor-suppressor gene and the IGF2 growth factor. Hypermethylation of this DMR - and subsequently of the H19 promoter region - is a major cause of the clinical features of gigantism and/or asymmetry seen in Beckwith-Wiedemann syndrome or in isolated hemihypertrophy. Here, we report a series of patients with hypomethylation of the H19 locus. Their main clinical features of asymmetry and growth retardation are the opposite of those seen in patients with hypermethylation of this region. In addition, we show that complete hypomethylation of the H19 promoter is found in two of three patients with the full clinical spectrum of Silver-Russell syndrome. This syndrome is also characterized by growth retardation and asymmetry, among other clinical features. We conclude that patients with these clinical features should be analyzed for H19 hypomethylation.
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页码:604 / 614
页数:11
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