Silver-Russell syndrome in a girl born after in vitro fertilization: partial hypermethylation at the differentially methylated region of PEG1/MEST
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Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19.
Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA.
Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient.
Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART.
KeywordsHypermethylation Imprinting In vitro fertilization PEG1/MEST Silver-Russell syndrome
This work was supported by a grant for Child Health and Development (17C-2) and a grant for Research on Children and Families from the Ministry of Health, Labor, and Welfare.
- 5.Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Le Merrer M, Burglen L, Bertrand AM, Netchine I, Le Bouc Y: Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet. 2005;37:1003–7.PubMedCrossRefGoogle Scholar
- 12.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: Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am J Hum Genet 2006;78:604–14.PubMedCrossRefGoogle Scholar
- 15.Kobayashi S, Uemura H, Kohda T, Nagai T, Chinen Y, Naritomi K, Kinoshita EI, Ohashi H, Imaizumi K, Tsukahara M, Sugio Y, Tonoki H, Kishino T, Tanaka T, Yamada M, Tsutsumi O, Niikawa N, Kaneko-Ishino T, Ishino F: No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients. Am J Med Genet 2001;104:225–31.PubMedCrossRefGoogle Scholar