Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype.
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.
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Jet
J
Bliek
Paulien
P
Terhal
Marie-José
MJ
van den Bogaard
Saskia
S
Maas
Ben
B
Hamel
Georgette
G
Salieb-Beugelaar
Marleen
M
Simon
Tom
T
Letteboer
Jasper
J
van der Smagt
Hester
H
Kroes
Marcel
M
Mannens
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D015342:DNA Probes; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D010641:Phenotype; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D013577:Syndrome
D015342:DNA Probes; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated